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Sample records for local allergoid immunotherapy

  1. [Specific immunotherapy with depigmented allergoids].

    Science.gov (United States)

    Klimek, L; Thorn, C; Pfaar, O

    2010-01-01

    Specific immunotherapy is the only available causative treatment for IgE-mediated allergic conditions. The state of the art is treatment via the subcutaneous route with crude extracts in a water solution, with physically linked (semidepot) extracts or chemically modified semidepot extracts (allergoids). A relatively new purification method combines depigmentation followed by polymerization with glutaraldehyde. This modification results in increased tolerance with a reduction in both local and systemic adverse effects. As controlled clinical trials have shown, the effectiveness is comparable to that of specific immunotherapy with crude allergen extracts. Recent data suggest that the modified polymerized allergoids allow a safe rush titration in a few days or even in 1 day (ultra-rush titration).

  2. A review of allergoid immunotherapy: is cat allergy a suitable target?

    Science.gov (United States)

    Nguyen, Nhung T; Raskopf, Esther; Shah-Hosseini, Kija; Zadoyan, Gregor; Mösges, Ralph

    2016-01-01

    To modify the course of allergy, different types of specific allergen immunotherapy have been developed such as sublingual immunotherapy and subcutaneous immunotherapy with native allergens or subcutaneous immunotherapy with polymerized allergoids. However, the optimal specific immunotherapy, especially for cat allergy, remains undetermined. Few studies investigating immunotherapy in cat allergy have been published, and the risk of serious adverse reactions and systemic reactions has often been an important issue. Monomeric allergoids have lower allergenic potential while their immunogenicity remains constant, resulting in excellent safety with notable efficacy. Specific immunotherapy with monomeric allergoids could, therefore, be of high value, especially in cat allergy as well as other types of allergy, and bring relief to a great community of patients.

  3. Quality requirements for allergen extracts and allergoids for allergen immunotherapy.

    Science.gov (United States)

    Zimmer, J; Bonertz, A; Vieths, S

    2017-12-01

    All allergen products for allergen immunotherapy currently marketed in the European Union are pharmaceutical preparations derived from allergen-containing source materials like pollens, mites and moulds. Especially this natural origin results in particular demands for the regulatory requirements governing allergen products. Furthermore, the development of regulatory requirements is complicated by the so far missing universal link between certain quality parameters, in particular biological potency, on the one hand and clinical efficacy on the other hand. As a consequence, each allergen product for specific immunotherapy has to be assessed individually for its quality, safety and efficacy. At the same time, biological potency of allergen products is most commonly determined using IgE inhibition assays based on human sera relative to product-specific in house references, ruling out full comparability of products from different manufacturers. This review article aims to summarize the current quality requirements for allergen products including the special requirements implemented for control of chemically modified allergen extracts (allergoids). Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  4. [The use of Russian allergoids for the specific immunotherapy of pollinosis].

    Science.gov (United States)

    Fradkin, V A; Roshal', N I; Goriachkina, L A; Nikonorova, M V; Astaf'eva, N G; Luss, L V; Raĭkis, V N

    1993-01-01

    For three years 128 pollinosis patients received specific immunotherapy with cereals, weed and tree pollen allergens manufactured by the Scientific and Industrial Amalgamation "Allergen" (Stavropol). For comparison, a group of 42 patients was treated with the corresponding allergens according to the commonly used treatment scheme. Patients who had earlier undergone treatment with water-saline extracts of allergens, that proved to be ineffective, formed a special group. In sensitive patients reaction to the skin test with allergoids was by half less pronounced than reaction to the skin test with allergens. In allergometric titration on the nasal mucosa, reaction to the introduction of allergoids could be registered when they were used at a 10- to 100-fold higher concentration than allergens. The course of specific immunotherapy with allergoids was found to lead to a decrease in the level of allergen-specific IgE antibodies (p > 0.05) and total IgE (p allergoids was more effective than that with water-saline extracts of allergens. The use of allergoids made it possible to prescribe specific immunotherapy to a wider circle of patients.

  5. Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy.

    Science.gov (United States)

    Lund, L; Henmar, H; Würtzen, P A; Lund, G; Hjortskov, N; Larsen, J N

    2007-04-01

    Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid

  6. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract.

    Science.gov (United States)

    Bousquet, J; Hejjaoui, A; Skassa-Brociek, W; Guérin, B; Maasch, H J; Dhivert, H; Michel, F B

    1987-10-01

    Forty-five grass pollen-allergic patients were randomly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis. Eleven patients were treated with placebo (group 1), 19 patients (group 2) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure, and 15 other patients were treated with a standardized orchard grass-pollen extract (group 3). Because of a different immunotherapy schedule, only patients placed in groups 1 and 2 received the extracts in a double-blind fashion. Rush immunotherapy was performed in 3 to 6 days, and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season. During the season, a coseasonal treatment was administered. Systemic reactions occurred during the rush protocol in 36.8% of patients treated with allergoid and 20% of patients who received the standardized extract. Only patients treated with allergoid had systemic reactions during maintenance dose. The reactions observed with the standardized extract were more severe. Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units. Symptoms and medication scores during the peak of the season were analyzed. Patients treated with the standardized allergen had a significant reduction of the number of days of symptoms during the month of June (9.5 +/- 6.7 days; p less than 0.005) and of medication scores (1.3 +/- 1.4; p less than 0.01) compared to patients receiving placebo (19.4 +/- 8.1 days; medication score, 2.8 +/- 2.1).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Single-course specific immunotherapy with mixed pollen allergoids: results of a multi-centre study.

    Science.gov (United States)

    Drachenberg, K J; Pröll, S; Urban, E; Woroniecki, S R

    2003-01-01

    A short-term immunotherapy vaccine for the treatment of pollen allergy has been developed utilising L-tyrosine adsorbed allergoids. The reduced number of injections could provide advantages over long-term therapy schedules. This would improve compliance and support application of specific immunotherapy (SIT) to a greater extent. We report a multicenter study to evaluate the efficacy and safety of this treatment in a clinical practice setting. Patients (n = 1808) with a diagnosis of sensitivities to various pollens and symptoms of allergic asthma and/or allergic rhinitis and/or allergic conjunctivitis were selected. The vaccine formulation was made up according to individual sensitivities and contained L-tyrosine adsorbed allergoids. The patients were treated with a 3-injection initial course followed by a 3-injection maintenance course. Efficacy was measured by consumption of symptomatic anti-allergic medication compared with that in the previous season and by physician assessment using a 5-point scale. All adverse events were recorded. Efficacy was demonstrated by a considerable decrease in regular and frequent use of medication compared with that in the previous season (p allergoid/L-tyrosine vaccine in a clinical practice setting provided a high level of efficacy with a low incidence of mainly mild adverse events.

  8. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.

    Science.gov (United States)

    Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

    2008-09-01

    Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

  9. Specific immunotherapy with allergoids in atopic subjects, hyporeactive to other vaccines.

    Science.gov (United States)

    Vargiu, G; Valcurone, G; Agostoni, A; Sacchi, G; Tassi, G C

    1986-01-01

    Allergoids comply with the therapeutic requirement to reach high doses of the injected allergen, since the modifications of the allergens cause a loss of allergenicity, though the immunogenicity is being retained. Considering that it is possible to use a starting dose 40 times higher in comparison with retard vaccines, we thought it very expedient to treat with allergoids 18 patients allergic to parietaria, and 12 patients allergic to grass pollen, who had shown no clinical improvement after immunotherapy, lasting for at least three years with retard vaccines. The therapeutic results obtained are the following: improvement in 66% of the parietaria allergic patients after the first year, and of the 72% in the second year, of the 75% of the grass pollen allergic patients after the first year and of the 83% in the second year. They can be interpreted as due to the fact that such patients are always poorly reactive to the doses of allergens commonly present in retard vaccines. On the contrary, they do react to allergoids, both due to the high amount of allergen administered, and to the fact that polymerization brings about a stronger epitopic expression matched by a higher immunogenic activity. Moreover, the data are also indicative for a good relationship between the antibody titer of antigen-specific blocking IgG and the clinical effectiveness valued by means of symptom and medication scores.

  10. Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children.

    Science.gov (United States)

    Rosewich, M; Schulze, J; Eickmeier, O; Telles, T; Rose, M A; Schubert, R; Zielen, S

    2010-06-01

    Specific immunotherapy (SIT) is a well-established and clinically effective treatment for allergic diseases. A pollen allergoid formulated with the T helper type 1 (Th1)-inducing adjuvant monophosphoryl lipid A (MPL) facilitates short-term SIT. Little is known about mechanisms of tolerance induction in this setting. In a prospective study, 34 patients allergic to grass pollen (25 male, nine female, median age 10.2 years) received a total of 44 SIT courses (20 in the first, 24 in the second) with MPL-adjuvanted pollen allergoids. Immunogenicity was measured by levels of specific immunoglobulin G (IgG(grass)) and IgG4(grass) by antibody blocking properties on basophil activation, and by induction of CD4(+), CD25(+) and forkhead box P3 (FoxP3(+)) regulatory T cells (T(reg)). Specific IgG and IgG4 levels increased only slightly in the first year of SIT. In the second year these changes reached significance (P allergoids formulated with the Th1-inducing adjuvant MPL needs at least two courses to establish tolerance.

  11. 11 Efficacy and Tolerability of HDM Injective Immunotherapy With Monomeric Allergoid

    Science.gov (United States)

    Compalati, Enrico; Atzeni, Isabella; Cabras, Sergio; Fancello, Paolo; Gaspardini, Giulio; Longo, Rocco; Patella, Vincenzo; Tore, Giorgio

    2012-01-01

    Background Subcutaneous immunotherapy (SCIT) is an effective treatment of respiratory allergy and carbamylated monomeric allergoids (monoids), by virtue of their reduced IgE-binding activity, resulted clinically safe by sublingual administration. Purpose of this study was to investigate the efficacy and tolerability of immunotherapy with house dust mites (HDM) monoid administered by injective route in patients with allergic rhinoconjunctivitis (AR). Methods A preparation of 0.70 mL of 10 BU/mL containing modified extract with 50% Dermatophagoides pteronyssinus and 50% Dermatophagoides farinae (amount of major allergen: 4 μg of group 1 per milliliter) was delivered monthly for 12 months, following a 5-week build-up induction phase (0.10–0.20–0.30–0.50–0.70 mL), to 58 patients (60% males, mean age 25.1 ± 12.7) suffering from AR due to mites for at least 2 years, whereas 60 patients with similar baseline characteristics were observed as controls. All patients were allowed to assume traditional drug therapy for their condition. At the end of the study changes from baseline in symptoms scores, in number of days with drug assumption, in severity of AR (according to ARIA classification) were compared between the 2 groups; moreover an overall assessment of clinical efficacy and tolerability was based on patients' and physicians' judgements (unsatisfactory, mild, good, optimal). Results In respect to baseline both groups showed, after 1 year, an improvement in symptoms score (P allergoid was associated with a significant clinical benefit observed through objective and subjective outcomes; the traditional safety of monomeric allergoids was confirmed by the subjective judgements of tolerability.

  12. Artemisia vulgaris pollen allergoids digestibility in the simulated conditions of the gastrointestinal tract

    OpenAIRE

    RATKO M. JANKOV; NATALIJA DJ. POLOVIC; MARIJA DJ. GAVROVIC-JANKULOVIC; LIDIJA BURAZER; DANICA DJERGOVIC-PETROVIC; OLGA VUCKOVIC; OLIKA DROBNJAK; ZORICA SPORCIC; MARINA ATANASKOVIC-MARKOVIC; RATKO M. JANKOV

    2006-01-01

    Chemically modified allergens (allergoids) have found use in both traditional and novel forms of immunotherapy of allergic disorders. Novel forms of immunotherapy include local allergen delivery, via the gastrointestinal tract. This study conveys the gastrointestinal stability of three types ofmugwort pollen allergoids under simulated conditions of the gut. Allergoids of the pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, succinic and maleic anhydride. Gastro...

  13. [Cluster-immunotherapy in seasonal allergic rhinitis: safety aspects of induction therapy with depot allergoids (Purethal)].

    Science.gov (United States)

    Hansen, I; Hörmann, K; Stuck, B A; Schneider-Gêne, S; Mösges, R; Klimek, L

    2003-08-01

    Specific immunotherapy (SIT) represents the only specific treatment that can be offered to allergic patients apart from allergen avoidance. SIT has been widely used in pollen allergic rhinitis. Clinical efficacy has been demonstrated in several controlled clinical trials and depends on the specific allergen the individual patient is sensitive to, the quality and total amount of allergen applied, and the SIT schedule. In classic SIT, gradually increasing dosages of the allergen extract are injected subcutaneously. Several dosage schedules for subcutaneous SIT can be applied. In Cluster-SIT, 2 - 3 injections per day of treatment are given once a week during induction treatment. In this study, we investigated 64 patients (33 female, 31 male) from 18 to 54 years (26.9 +/- 5.1 years) in terms of side-effects of Cluster-SIT during induction treatment. The total amount of enlarged local reactions (> grade 1) was n = 77 or 15.2 % of all injections. Of these, 68 (88 %) were classified as immediate reactions, 8 (11 %) were late phase reactions and 1 (1 %) was immediate as well as late phase reaction. Of all enlarged local reactions, 48 (62 %) were grade 1 reactions, 13 (17 %) were grade 2 reactions, 13 (17 %) were grade 3 reactions and 1 (1 %) was a grade 4 reaction. The total amount of systemic reactions was n = 22 or 4.3 % of all injections. Of these, 19 (86 %) were classified as immediate reactions, 3 (14 %) were delayed reactions. Of all systemic reactions, 18 (82 %) were grade 1 reactions and 4 (18 %) grade 2 reactions. Grade 3 or grade 4 reactions did not occur. There were no differences in gender or age regarding the occurrence of side effects (all p > 0.05). Frequency and severity of adverse side effects in Cluster-SIT correspond to those in other dosage schedules. On behalf of security aspects, Cluster-SIT could become an interesting alternative dosage schedule for dose increase during SIT. Furthermore, in Cluster-SIT with allergoids, induction treatment can be

  14. Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis

    Science.gov (United States)

    Babakhin, Alexander; Andreev, Sergey; Nikonova, Alexandra; Shilovsky, Igor; Buzuk, Andrey; Elisyutina, Olga; Fedenko, Elena; Khaitov, Musa

    2015-01-01

    Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD. PMID:26275152

  15. Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

    Science.gov (United States)

    Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

    2008-01-01

    The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (pallergoids are utilized.

  16. Health economic comparison of SLIT allergen and SCIT allergoid immunotherapy in patients with seasonal grass-allergic rhinoconjunctivitis in Germany.

    Science.gov (United States)

    Verheggen, Bram G; Westerhout, Kirsten Y; Schreder, Carl H; Augustin, Matthias

    2015-01-01

    Allergoids are chemically modified allergen extracts administered to reduce allergenicity and to maintain immunogenicity. Oralair® (the 5-grass tablet) is a sublingual native grass allergen tablet for pre- and co-seasonal treatment. Based on a literature review, meta-analysis, and cost-effectiveness analysis the relative effects and costs of the 5-grass tablet versus a mix of subcutaneous allergoid compounds for grass pollen allergic rhinoconjunctivitis were assessed. A Markov model with a time horizon of nine years was used to assess the costs and effects of three-year immunotherapy treatment. Relative efficacy expressed as standardized mean differences was estimated using an indirect comparison on symptom scores extracted from available clinical trials. The Rhinitis Symptom Utility Index (RSUI) was applied as a proxy to estimate utility values for symptom scores. Drug acquisition and other medical costs were derived from published sources as well as estimates for resource use, immunotherapy persistence, and occurrence of asthma. The analysis was executed from the German payer's perspective, which includes payments of the Statutory Health Insurance (SHI) and additional payments by insurants. Comprehensive deterministic and probabilistic sensitivity analyses and different scenarios were performed to test the uncertainty concerning the incremental model outcomes. The applied model predicted a cost-utility ratio of the 5-grass tablet versus a market mix of injectable allergoid products of € 12,593 per QALY in the base case analysis. Predicted incremental costs and QALYs were € 458 (95% confidence interval, CI: € 220; € 739) and 0.036 (95% CI: 0.002; 0.078), respectively. Compared to the allergoid mix the probability of the 5-grass tablet being the most cost-effective treatment option was predicted to be 76% at a willingness-to-pay threshold of € 20,000. The results were most sensitive to changes in efficacy estimates, duration of the pollen season, and

  17. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. II. Comparison between parameters assessing the efficacy of immunotherapy.

    Science.gov (United States)

    Bousquet, J; Maasch, H; Martinot, B; Hejjaoui, A; Wahl, R; Michel, F B

    1988-09-01

    Specific immunotherapy is effective in alleviating symptoms in grass pollen-induced rhinitis, but there are no clear data demonstrating a correlation between symptom-medication scores and objective parameters. Twenty-five patients taking part in a double-blind, placebo-controlled immunotherapy with mixed grass pollen-formalinized allergoids were studied. All patients had the same investigations. Symptom-medication scores were significantly (p less than 0.005, Mann-Whitney U test) reduced in the treated group by comparison to the placebo-treated patients. Nasal challenges performed with threefold increasing numbers of orchard grass-pollen grains demonstrated that patients treated with allergoid tolerated a significantly (p less than 0.005, Wilcoxon W test) greater number of grains after treatment, whereas there was no mean difference in the placebo-treated patients. There was a significant (p less than 0.005, Spearman rank-correlation) correlation between nasal challenges and symptom scores during the season. The skin prick test end point was significantly (p less than 0.001, Wilcoxon W test) reduced after treatment in the allergoid-treated group and remained unchanged in the placebo-treated group. There was a significant (p less than 0.001) correlation between the skin prick test end point and symptom scores during the season. Serum grass-pollen IgG titrated by a solid-phase radioimmunoassay with Staphylococcus A protein was significantly (p less than 0.01, Wilcoxon W test) increased after treatment with allergoid, but there was no significant correlation between IgG titer and symptom scores during the season. Serum grass-pollen IgE increased (p less than 0.04, Wilcoxon W test) in the treated group but there was no correlation with symptom scores.

  18. The adsorption of allergoids and 3-O-desacyl-4'-monophosphoryl lipid A (MPL®) to microcrystalline tyrosine (MCT) in formulations for use in allergy immunotherapy.

    Science.gov (United States)

    Bell, A J; Heath, M D; Hewings, S J; Skinner, M A

    2015-11-01

    Infectious disease vaccine potency is affected by antigen adjuvant adsorption. WHO and EMA guidelines recommend limits and experimental monitoring of adsorption in vaccines and allergy immunotherapies. Adsorbed allergoids and MPL® in MATA-MPL allergy immunotherapy formulations effectively treat IgE mitigated allergy. Understanding vaccine antigen adjuvant adsorption allows optimisation of potency and should be seen as good practice; however current understanding is seldom applied to allergy immunotherapies. The allergoid and MPL® adsorption to MCT in MATA-MPL allergy immunotherapy formulations was experimental determination using specific allergen IgE allerginicity and MPL® content methods. Binding forces between MPL® and MCT were investigated by competition binding experiments. MATA-MPL samples with different allergoids gave results within 100-104% of the theoretical 50μg/mL MPL® content. Unmodified drug substance samples showed significant desirable IgE antigenicity, 1040-170 QAU/mL. MATA-MPL supernatant samples with different allergoids gave results of ≤2 μg/mL MPL® and ≤0.1-1.4 QAU/mL IgE antigenicity, demonstrating approximately ≥96 & 99% adsorption respectively. Allergoid and MPL® adsorption in different MATA-MPL allergy immunotherapy formulations is consistent and meets guideline recommendations. MCT formulations treated to disrupt electrostatic, hydrophobic and ligand exchange interactions, gave an MPL® content of ≤2 μg/mL in supernatant samples. MCT formulations treated to disrupt aromatic interactions, gave an MPL® content of 73-92 μg/mL in supernatant samples. MPL® adsorption to l-tyrosine in MCT formulations is based on interactions between the 2-deoxy-2-aminoglucose backbone on MPL® and aromatic ring of l-tyrosine in MCT, such as C-H⋯π interaction. MCT could be an alternative adjuvant depot for some infectious disease antigens. Copyright © 2015. Published by Elsevier Inc.

  19. Carbamylated monomeric allergoids as a therapeutic option for sublingual immunotherapy of dust mite- and grass pollen-induced allergic rhinoconjunctivitis: a systematic review of published trials with a meta-analysis of treatment using Lais® tablets.

    Science.gov (United States)

    Mösges, R; Ritter, B; Kayoko, G; Allekotte, S

    2010-10-01

    Lais® allergoid tablets contain allergens that are modified by carbamylation. Due to their modified chemical structure, they are suitable for sublingual immunotherapy (SLIT) (13, 16, 17, 24). Based on their small molecule size of 12 to 40 kDa, they can be easily absorbed via the oral mucosa (1). In this review, we studied the efficacy of SLIT with carbamylated monomeric allergoid tablets in the treatment of grass pollen- and dust mite-induced allergic rhinoconjunctivitis on the basis of symptom and medication score improvements. Following a selective internet and databank search, six trials-some placebo-controlled-regarding the treatment of grass pollen- (n = 266) and dust mite-induced (n = 241) allergic rhinoconjunctivitis were used to draw conclusions regarding the clinical efficacy of allergoid tablets. The primary endpoints in these trials were decreases in the need for allergy medications and/or reductions in the occurrence of rhinoconjunctivitis symptoms. Data was recorded from patient diaries regarding their symptoms and medications used and conclusions were then drawn about the effectiveness and tolerabieity of Lais® tablets. The average improvement in symptom score in three trials of grass pollen allergy treatment was 34% in comparison to the placebo group. The treatment of dust mite-induced rhinoconjunctivitis produced an average symptom score improvement of 22% compared to the placebo or control groups. The intake of symptomatic rescue medication during allergoid tablet therapy declined. Treatment of grass pollen allergies and dust mite-induced rhinoconjunctivitis showed an average medication score improvement of 49% and 24%, respectively. Few side effects were documented in the trials and predominantly local effects were observed. Severe systemic side effects did not occur. On the basis of the trial results summarized in this review, we suggest that SLIT using Lais® sublingual tablets is an effective and well-tolerated form of treatment.

  20. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. IV. Comparison of the safety and efficacy of two dosages of a high-molecular-weight allergoid.

    Science.gov (United States)

    Bousquet, J; Hejjaoui, A; Soussana, M; Michel, F B

    1990-02-01

    Specific immunotherapy is still widely used in grass-pollen allergy, but its side effects may limit its use. We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind, placebo-controlled study. Eighteen patients received placebo, 19 received the low-dose schedule (maximal dose: 2000 PNU) and 20 received the high-dose schedule (maximal dose: 10,000 PNU). Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU. Before the onset of the pollen season, patients had a nasal challenge with orchard grass-pollen grains, a skin test titration, and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo. Symptoms and medications for rhinitis and asthma were studied during the season, and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms. There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges. High-molecular-weight allergoids are safe and effective.

  1. Allergoid-specific T-cell reaction as a measure of the immunological response to specific immunotherapy (SIT) with a Th1-adjuvanted allergy vaccine.

    Science.gov (United States)

    von Baehr, V; Hermes, A; von Baehr, R; Scherf, H P; Volk, H D; Fischer von Weikersthal-Drachenberg, K J; Woroniecki, S

    2005-01-01

    Specific immunotherapy (SIT) is believed to modulate CD4+ T-helper cells. In order to improve safety, SIT vaccines are often formulated with allergoids (chemically modified allergens). Interaction between T-cells and allergoids is necessary to influence cellular cytokine expression. There have been few reports on identification the early cellular effects of SIT. Patients allergic to grass and/or mugwort pollen (n= 21) were treated with a 4-shot allergy vaccine (Pollinex Quattro) containing appropriate allergoids (grass/rye and/or mugwort) adsorbed to L-tyrosine plus a Th1 adjuvant, monophosphoryl lipid A (MPL). Fourteen grass-allergic patients served as untreated controls. Using the peripheral blood mononuclear cells of these patients, an optimized lymphocyte transformation test (LTT) was employed to monitor the in vitro proliferative response of T-cells to an allergoid challenge (solubilised Pollinex Quattro) before the first and last injection and then 2 and 20 weeks after the final injection. Control challenges utilised preparations of a similar pollen vaccine without the adjuvant MPL and a tree pollen vaccine with and without MPL. The LTT showed increased LTT stimulation indices (SI) in 17/20 SIT patients when the solublised vaccine preparation was used as a challenge before the last injection and 2 weeks after, in comparison to pre-treatment levels. Twenty weeks after therapy, the SI decreased to baseline level. A vaccine challenge without MPL gave lower SI levels. A challenge of a clinically inappropriate tree allergoid vaccine gave no response, and a nontreated group also showed no response. Following a short-course SIT adjuvated with MPL, challenges of allergoids were shown to activate allergen-specific T cells in vitro. There was an additional stimulating effect when the challenge was in combination with MPL. There were no non-specific effects of MPL, shown by the tree allergoid/MPL control. The timing of the response was closely correlated to the

  2. Efficacy and tolerability of short-term specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and adolescents.

    Science.gov (United States)

    Drachenberg, K J; Heinzkill, M; Urban, E; Woroniecki, S R

    2003-01-01

    Specific immunotherapy (SIT) with pollen allergoids formulated with the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa) has shown good efficacy and tolerability in the treatment of pollen allergies in adults. The aim of this study was to evaluate this treatment in children and adolescents aged 6-17 years old who were sensitive to grass/rye or tree pollens. An open, multicenter study was performed using 90 children and adolescents. The patients received four subcutaneous injections of grass/rye (n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing MPL adjuvant. Efficacy was measured by symptom and medication scoring, skin prick test reactivity and IgG/IgE antibody responses. Tolerability was monitored by recording adverse events. Both grass/rye and tree pollen treatment groups showed significant reductions in symptom scores and anti-allergic medication use compared with the previous pollen seasons (p allergoids adsorbed to L-tyrosine and with MPL adjuvant was shown to be effective with good tolerability. The treatment compared favorably with previous studies in adults.

  3. A novel and well tolerated mite allergoid subcutaneous immunotherapy: evidence of clinical and immunologic efficacy

    Science.gov (United States)

    Roger, Albert; Depreux, Nathalie; Jurgens, Yani; Heath, Matthew D; Garcia, Gloria; Skinner, Murray A

    2014-01-01

    Allergy to house dust mite is one of the most common causes of allergic rhinitis. A novel tyrosine-adsorbed, modified allergen product, Acarovac Plus, developed for the treatment of perennial mite allergy seeks to address the underlying cause of allergic rhinitis in this instance. One of two dosing regimens may be used, either the Conventional Regimen or the Cluster Regimen. We sought to compare the efficacy and safety of a specific immunotherapy, developed for the treatment of perennial mite allergy, administered under a Conventional and Clustered dosing schedule in patients with persistent allergic rhinitis. Thirty adult patients, between 18 and 65 years old, with allergic rhinitis and/or asthma secondary to hypersensitivity to Dermatophagoides pteronyssinus were administered with either conventional or cluster initial regime, with a final visit one week after the last dose administration. The efficacy to the Conventional and Cluster regimens was measured using a Nasal Challenge Test monitoring clinical symptoms and peak nasal inspiratory flow. Total IgE, serum-specific inmunoglobulins (IgE and IgG4) to Dermatophagoides pteronyssinus and relevant cytokines (IFN-γ, IL-4, IL-5, IL-10 and IL-13) were assessed. A Satisfaction Questionnaire (TSQM) was completed after each patient's final visit. The tolerability of the vaccine was assessed monitoring adverse reactions. No adverse events were recorded in either conventional or cluster regime. The specific Nasal Challenge Test led to a decrease in symptom scores and a significant decrease in mean nasal peak inspiratory flow drop was recorded in both dosing regimen groups. A significant increase in IgG4-specific antibody titres was assessed. No significant changes were observed in concentrations of total IgE, specific IgE or cytokines (IFN-γ, IL-4, IL-5, IL-10 and IL-13). Patients declared themselves most satisfied in relation to “Secondary effects”, with high overall satisfaction in both groups. Cluster and

  4. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. III. Efficacy and safety of unfractionated and high-molecular-weight preparations in rhinoconjunctivitis and asthma.

    Science.gov (United States)

    Bousquet, J; Maasch, H J; Hejjaoui, A; Skassa-Brociek, W; Wahl, R; Dhivert, H; Michel, F B

    1989-10-01

    Specific immunotherapy with unmodified formalinized allergoids is effective in grass-pollen allergy, but systemic reactions have been observed. A high-molecular-weight formalinized allergoid (HMW-GOID) was fractionated by gel filtration, retaining molecules of greater than 85,000 daltons in the expectation of improving safety without sacrificing efficacy. HMW-GOID and unfractionated allergoid (GOID) had a similar allergenic activity assessed by RAST inhibition, but the HMW-GOID preparation was 65 times less reactive when it was tested by skin prick test than the GOID preparation. A double-blind, placebo-controlled study was carried out in grass pollen-allergic patients with placebo (14 patients), GOID (15 patients), and HMW-GOID (13 patients). An additional group of 18 patients was treated by a rush schedule with a standardized orchard grass-pollen extract. A similar mean cumulative dose was administered with both allergoids. The fractionated allergoid only elicited minor systemic reactions similar to reactions elicited by placebo, whereas 20% of patients treated by GOID and 5.5% of patients receiving the standardized extract had a severe systemic reaction. For rhinitis, conjunctivitis, and asthma, the HMW-GOID and the standardized extract had a similar efficacy, significantly greater than placebo. GOID was less effective than the other two active treatments but was significantly more effective than placebo treatment for asthma and conjunctivitis.

  5. Mite allergoids coupled to nonoxidized mannan from Saccharomyces cerevisae efficiently target canine dendritic cells for novel allergy immunotherapy in veterinary medicine.

    Science.gov (United States)

    Soria, Irene; Alvarez, Javier; Manzano, Ana I; López-Relaño, Juan; Cases, Bárbara; Mas-Fontao, Ana; Cañada, F Javier; Fernández-Caldas, Enrique; Casanovas, Miguel; Jiménez-Barbero, Jesús; Palomares, Oscar; Viñals-Flórez, Luis M; Subiza, José L

    2017-08-01

    We have recently reported that grass pollen allergoids conjugated with nonoxidized mannan of Saccharomyces cerevisae using glutaraldehyde results in a novel hypoallergenic mannan-allergen complex with improved properties for allergen vaccination. Using this approach, human dendritic cells show a better allergen uptake and cytokine profile production (higher IL-10/IL-4 ratio) for therapeutic purposes. Here we aim to address whether a similar approach can be extended to dogs using canine dendritic cells. Six healthy Spanish Greyhound dogs were used as blood donors to obtain canine dendritic cells (DC) derived from peripheral blood monocytes. Allergens from Dermatophagoides farinae mite were polymerized and conjugated with nonoxidized mannan. Nuclear magnetic resonance (NMR), gel electrophoresis (SDS-PAGE), immunoblotting and IgE-ELISA inhibition studies were conducted to evaluate the main characteristics of the allergoid obtained. Mannan-allergen conjugate and controls were assayed in vitro for canine DC uptake and production of IL-4 and IL-10. The results indicate that the conjugation of D. farinae allergens with nonoxidized mannan was feasible using glutaraldehyde. The resulting product was a polymerized structure showing a high molecular weight as detected by NMR and SDS-PAGE analysis. The mannan-allergen conjugate was hypoallergenic with a reduced reactivity with specific dog IgE. An increase in both allergen uptake and IL-10/IL-4 ratio was obtained when canine DCs were incubated with the mannan-allergen conjugate, as compared with the control allergen preparations (unmodified D. farinae allergens and oxidized mannan-allergen conjugate). We conclude that hypoallergenic D. farinae allergens coupled to nonoxidized mannan is a novel allergen preparation suitable for canine allergy immunotherapy targeting dendritic cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Monoid sublingual immunotherapy.

    Science.gov (United States)

    Palma-Carlos, A G; Santos, A S; Branco-Ferreira, M; Pregal, A L; Palma-Carlos, M L

    2006-03-01

    Sublingual monoid immunotherapy with monomeric allergoids has been largely used in Europe in the last few years. An open trial of allergoid in tablets has been done in rhinitic patients allergic to house dust mites, grass pollens and Parietaria with clear improvement in clinics and drug consumption scores. In a second phase a double blind placebo controlled trial of grass pollens allergoids have been done in hay fever patients with significant decrease on the scores of rhinorrea, sneezing and conjunctivitis nasal steroid consumption and clinical score after serial nasal challenges. Monomeric allergoids are an efficace and safe immunotherapy in allergic rhinitis.

  7. Structural studies of novel glycoconjugates from polymerized allergens (allergoids) and mannans as allergy vaccines

    OpenAIRE

    Manzano, Ana I.; Cañada, F. Javier; Cases, Bárbara; Sirvent, Sofia; Soria-Castro, Irene; Palomares, O; Fernández-Caldas, E.; Casanovas, Miguel; Jiménez-Barbero, Jesús; Subiza, José L.

    2015-01-01

    Immunotherapy for treating IgE-mediated allergies requires high doses of the corresponding allergen. This may result in undesired side effects and, to avoid them, hypoallergenic allergens (allergoids) polymerized with glutaraldehyde are commonly used. Targeting allergoids to dendritic cells to enhance cell uptake may result in a more effective immunotherapy. Allergoids coupled to yeast mannan, as source of polymannoses, would be suitable for this purpose, since mannose-binding receptors are e...

  8. Local immunological mechanisms of sublingual immunotherapy.

    Science.gov (United States)

    Allam, Jean-Pierre; Novak, Natalija

    2011-12-01

    To summarize novel insights into the immunological mechanisms of sublingual immunotherapy (SLIT). Within the recent decades, several alternative noninvasive allergen application strategies have been investigated in allergen-specific immunotherapy (AIT), of which intra-oral allergen application to sublingual mucosa has been proven to be well tolerated and effective. To date, SLIT is widely accepted by most allergists as an alternative option to conventional subcutaneous immunotherapy (SCIT). Although detailed immunological mechanisms remain to be elucidated, much scientific effort has been made to shed some light on local and systemic immunological responses to SLIT in mice as well as humans. Only a few studies focused on the detailed mechanisms following allergen application to the oral mucosa as part of the sophisticated mucosal immunological network. Within this network, the pro-tolerogenic properties of local antigen-presenting cells (APCs) such as dendritic cells - which are able to enforce tolerogenic mechanisms and to induce T-cell immune responses - play a central role. Further on, basic research focused not only on the immune response in nasal and bronchial mucosa but also on the systemic T-cell immune response. Thus, much exiting data have been published providing a better understanding of immunological features of SLIT but far more investigations are necessary to uncover further exciting details on the key mechanisms of SLIT.

  9. New routes of allergen immunotherapy.

    Science.gov (United States)

    Aricigil, Mitat; Muluk, Nuray Bayar; Sakarya, Engin Umut; Sakalar, Emine Güven; Senturk, Mehmet; Reisacher, William R; Cingi, Cemal

    2016-11-01

    Allergen immunotherapy is the only cure for immunoglobulin E mediated type I respiratory allergies. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are the most common treatments. In this article, we reviewed new routes of allergen immunotherapy. Data on alternative routes to allow intralymphatic immunotherapy (ILIT), epicutaneous immunotherapy (EPIT), local nasal immunotherapy (LNIT), oral immunotherapy (OIT), and oral mucosal immunotherapy (OMIT) were gathered from the literature and were discussed. ILIT features direct injection of allergens into lymph nodes. ILIT may be clinically effective after only a few injections and induces allergen-specific immunoglobulin G, similarly to SCIT. A limitation of ILIT is that intralymphatic injections are required. EPIT features allergen administration by using patches mounted on the skin. EPIT seeks to target epidermal antigen-presenting Langerhans cells rather than mast cells or the vasculature; this should reduce both local and systemic adverse effects. LNIT involves the spraying of allergen extracts into the nasal cavity. Natural or chemically modified allergens (the latter, termed allergoids, lack immunoglobulin E reactivity) are prepared in a soluble form. OIT involves the regular administration of small amounts of a food allergen by mouth and commences with low oral doses, which are then increased as tolerance develops. OMIT seeks to deliver allergenic proteins to an expanded population of Langerhans cells in the mucosa of the oral cavity. ILIT, EPIT, LNIT, OIT, and OMIT are new routes for allergen immunotherapy. They are safe and effective.

  10. Allergoids for allergy treatment.

    Science.gov (United States)

    Carnes, Jeronimo; Gallego, Maria T; Moya, Raquel; Iraola, Victor

    2018-02-21

    Background Chemically modified allergen extracts, known as allergoids, are commonly used for treating allergic patients. In general terms, the concept of allergoids implies allergen extracts with a reduction of their allergenicity maintaining their immunogenicity. Different methods to obtain allergoids have been developed in the past years, opening attractive lines of research. Objective To review the different approaches to allergoid development as well as their characterization, mechanism of action and efficacy and safety issues. Methods A revision and analysis of the different types of allergoids has been performed, with special attention to patents submitted and granted in the last years. Additionally, updated information about the mechanism of action and clinical evidence and safety of allergoids has been discussed. Results Principally, allergoids are obtained by the polymerization of native allergen extracts with aldehydes, including formaldehyde or glutaraldehyde. However, recent patents and publications about different chemical modifications have been presented, as well as about the use of new adjuvants with allergoids. Regarding the characterization, allergoids require more sophisticated analytical methods than native extracts, as a consequence of their properties and characteristics. Conclusion In the last years, the partial understanding of the mechanism of action and the generation of clinical evidence of different types of allergoids, linked to their excellent safety profile and their convenience for a quick build up phase, have made of allergoids an excellent product for allergy treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Artemisia vulgaris pollen allergoids digestibility in the simulated conditions of the gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    RATKO M. JANKOV

    2006-09-01

    Full Text Available Chemically modified allergens (allergoids have found use in both traditional and novel forms of immunotherapy of allergic disorders. Novel forms of immunotherapy include local allergen delivery, via the gastrointestinal tract. This study conveys the gastrointestinal stability of three types ofmugwort pollen allergoids under simulated conditions of the gut. Allergoids of the pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, succinic and maleic anhydride. Gastrointestinal tract conditions (saliva, and gastric fluid were simulated in accordance with the EU Pharmacopoeia. The biochemical and immunochemical properties of the derivatives following exposure to different conditions were monitored by determining the number of residual amino groups with 2,4,6-trinitrobenzenesulfonic acid, SDS PAGE, immunoblotting and inhibition of mugwort-specific IgE. Exposure to saliva fluid for 2 min did not influence the biochemical and immunochemical properties of the derivatives. In the very acidic conditions of the simulated gastric fluid, the degree of demaleylation and desuccinylation, even after 4 h exposure, was low, ranging from 10 to 30 %. The digestion patterns with pepsin proceeded rapidly in both the unmodified and modified samples. In all four cases, a highly resistant IgE-binding protein theMwof which was about 28 – 35 kD, was present. Within the physiological conditions, no new IgE binding epitopes were revealed, as demonstrated by immunoblot and CAP inhibition of the mugwort specific IgE binding. An important conclusion of this study is the stability of the modified derivatives in the gastrointestinal tract of patients, within physiological conditions. The means that they are suitable for use inmuch higher concentrations in local forms of immunotherapy than unmodified ones.

  12. Structural studies of novel glycoconjugates from polymerized allergens (allergoids) and mannans as allergy vaccines.

    Science.gov (United States)

    Manzano, Ana I; Javier Cañada, F; Cases, Bárbara; Sirvent, Sofia; Soria, Irene; Palomares, Oscar; Fernández-Caldas, Enrique; Casanovas, Miguel; Jiménez-Barbero, Jesús; Subiza, José L

    2016-02-01

    Immunotherapy for treating IgE-mediated allergies requires high doses of the corresponding allergen. This may result in undesired side effects and, to avoid them, hypoallergenic allergens (allergoids) polymerized with glutaraldehyde are commonly used. Targeting allergoids to dendritic cells to enhance cell uptake may result in a more effective immunotherapy. Allergoids coupled to yeast mannan, as source of polymannoses, would be suitable for this purpose, since mannose-binding receptors are expressed on these cells. Conventional conjugation procedures of mannan to proteins use oxidized mannan to release reactive aldehydes able to bind to free amino groups in the protein; yet, allergoids lack these latter because their previous treatment with glutaraldehyde. The aim of this study was to obtain allergoids conjugated to mannan by an alternative approach based on just glutaraldehyde treatment, taking advantage of the mannoprotein bound to the polymannose backbone. Allergoid-mannan glycoconjugates were produced in a single step by treating with glutaraldehyde a defined mixture of allergens derived from Phleum pratense grass pollen and native mannan (non-oxidized) from Saccharomyces cerevisae. Analytical and structural studies, including 2D-DOSY and (1)H-(13)C HSQC nuclear magnetic resonance spectra, demonstrated the feasibility of such an approach. The glycoconjugates obtained were polymers of high molecular weight showing a higher stability than the native allergen or the conventional allergoid without mannan. The allergoid-mannan glycoconjugates were hypoallergenic as detected by the IgE reactivity with sera from grass allergic patients, even with lower reactivity than conventional allergoid without mannan. Thus, stable hypoallergenic allergoids conjugated to mannan suitable for using in immunotherapy can be achieved using glutaraldehyde. In contrast to mannan oxidation, the glutaraldehyde approach allows to preserve mannoses with their native geometry, which may be

  13. Dose-response relationship of a new Timothy grass pollen allergoid in comparison with a 6-grass pollen allergoid.

    Science.gov (United States)

    Pfaar, O; Hohlfeld, J M; Al-Kadah, B; Hauswald, B; Homey, B; Hunzelmann, N; Schliemann, S; Velling, P; Worm, M; Klimek, L

    2017-11-01

    Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. To find the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in P. pratense-serum-specific IgG 4 and the incidence of adverse events (AEs). All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard-dose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured. © 2017 The Authors. Clinical & Experimental Allergy Published by John

  14. Immunotherapy

    Science.gov (United States)

    ... More Immunotherapy Immunotherapy Print Glossary Immunotherapy, also called biological therapy, utilizes your own immune system to fight cancer. ... she regularly tests your blood between and after treatment is completed to look ... of breath, a drop in blood pressure, an irregular heartbeat, chest pain ...

  15. Lymphocytic infiltration of bladder after local cellular immunotherapy.

    Science.gov (United States)

    Ingram, M; Bishai, M B; Techy, G B; Narayan, K S; Saroufeem, R; Yazan, O; Marshall, C E

    2000-01-01

    This is a case report of a patient who received cellular immunotherapy, in the form of local injections of autologous stimulated lymphocytes (ASL) into individual tumors in the urinary bladder. A major consideration in cellular immunotherapy being the ability of immune cells to reach all target areas, we hypothesized that direct delivery of effector cells into individual bladder tumors might assure such access. ASL were generated by exposing the patient's PBL to phytohemagglutinin and culturing them in the presence of IL-2 to expand the population. ASL were injected into the base of individual bladder tumors three times at intervals of 3 weeks. The patient died of a myocardial infarct, unrelated to cell therapy, 20 days after the third injection. An autopsy was performed. Histological sections of the bladder showed extensive lymphocytic infiltration of virtually the entire organ. No conclusions about the therapeutic efficacy of local immunotherapy using ASL are possible. Nevertheless, the observations reported, taken together with reports of therapeutic efficacy of other immunotherapy regimens in the management of bladder cancer, suggest that ready access of stimulated lymphocytes to all regions of the organ may account, in part, for the relatively high rate of therapeutic success reported for various immunotherapy regimens for this malignancy.

  16. Local Side Effects of Sublingual and Oral Immunotherapy.

    Science.gov (United States)

    Passalacqua, Giovanni; Nowak-Węgrzyn, Anna; Canonica, Giorgio Walter

    Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Characterization of allergoids.

    Science.gov (United States)

    Himly, Martin; Carnés, Jerónimo; Fernández-Caldas, Enrique; Briza, Peter; Ferreira, Fatima

    2009-01-01

    So far it has not been possible to measure the amount of major allergens in the complexes after chemical modification. Furthermore, the presence of minor allergens remained obscure, unless antibodies were successfully generated by animal immunization with allergoids and shown to be reactive with purified natural or recombinant allergens in immunological assays. Thus, we adapted and employed a set of physicochemical methods with the aim of elucidating the molecular size and allergen composition of allergoids. Using online-HPSEC light scattering and DLS, it was shown that two thirds of depigmented allergoid prepared from birch pollen extracts adopted a MW between 1000 and 2000 kDa. The question of reproducibility of the polymerization reaction was addressed by investigating four batches of P. pratense allergoid. Three out of the four batches contained 73 to 77% of polymerized molecules in the above-mentioned range of molecular sizes. One batch showed a significantly higher content of molecules with a MW exceeding 2 MDa. Analysis of allergen composition in B. alba allergoids revealed the presence of all relevant Bet v 1 isoforms and minor allergens except for Bet v 3 and Bet v 4, which was in good agreement with the allergens detected in the native extracts. It should be noted that Bet v 3 has not been detected at the protein level before. Similarly, good agreement in allergen composition between allergoid and native extract was also found for D. pteronyssinus. Presently, the European Directorate for Quality of Medicines and Healthcare (EDQM) is committed to the application of the 3R principles (i. e. replace, reduce, refine the use of animals) for the quality control of medicines wherever possible. This is reflected by the regular review of the monographs of the European Pharmacopoeia and the introduction of alternative tests. For instance, recently it was decided to replace the rabbit pyrogen test by an in vitro test. Furthermore, through the Biological

  18. Analysis of the CD4(+) T cell responses to house dust mite allergoid

    NARCIS (Netherlands)

    Kalinski, P.; Lebre, M. C.; Kramer, D.; de Jong, E. C.; van Schijndel, J. W. P. M.; Kapsenberg, M. L.

    2003-01-01

    Background: Modified allergen extracts (allergoids) with reduced IgE-binding capacity are successfully used in immunotherapy of atopic allergy. Their reduced T-cell stimulatory capacity is less well studied and is a subject of the present study. Methods: We compared the ability of native house dust

  19. Frequency of booster injections of allergoids.

    Science.gov (United States)

    Norman, P S; Creticos, P S; Marsh, D G

    1990-01-01

    In 1982, 43 ragweed-sensitive patients receiving maintenance injections of full doses of ragweed allergoid were selected for a study of the immunologic and clinical efficacy of booster injections only four times a year. These patients had participated for 2 to 7 years as part of a trial of mixes of up to four allergoids to common pollens in the mid-Atlantic area tailored to each patient's skin test sensitivity. They were divided into a group (21 patients) to receive injections every 3 months and a group (22 patients) to receive injections about every 6 weeks (eight injections per year). Patients were rerandomized after 1 year so that half of each original group switched to the alternate treatment, and this program was continued until after the ragweed season of 1985. Thirty-four patients were still under study the last year. Doses, per injection, were 100 allergoid units (1 allergoid unit equals 100 PNU) of each allergen in the mixture. Symptom scores during the 8 weeks of each of the four ragweed seasons were not significantly higher in the 3-month treated group. IgG antibody levels to Amb a I (antigen E) were followed until early 1984 and were not significantly different in the two groups, even though the 6-week treated patients received a two times higher cumulative dose per year. Rates of local and systemic reactions (percent of injections eliciting reactions) were not different in the groups, which means that the 3-month treated group had about half as many reactions by virtue of taking half as many injections.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial.

    Science.gov (United States)

    Chaker, A M; Al-Kadah, B; Luther, U; Neumann, U; Wagenmann, M

    2015-01-01

    The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.

  1. T cell reactivity with allergoids: influence of the type of APC.

    Science.gov (United States)

    Kahlert, H; Grage-Griebenow, E; Stüwe, H T; Cromwell, O; Fiebig, H

    2000-08-15

    The use of allergoids for allergen-specific immunotherapy has been established for many years. The characteristic features of these chemically modified allergens are their strongly reduced IgE binding activity compared with the native form and the retained immunogenicity. T cell reactivity of chemically modified allergens is documented in animals, but in humans indirect evidence of reactivity has been concluded from the induction of allergen-specific IgG during immunotherapy. Direct evidence of T cell reactivity was obtained recently using isolated human T cells. To obtain further insight into the mechanism of action of allergoids, we compared the Ag-presenting capacity of different APC types, including DC and macrophages, generated from CD14+ precursor cells from the blood of grass pollen allergic subjects, autologous PBMC, and B cells. These APC were used in experiments together with Phl p 5-specific T cell clones under stimulation with grass pollen allergen extract, rPhl p 5b, and the respective allergoids. Using DC and macrophages, allergoids exhibited a pronounced and reproducible T cell-stimulating capacity. Responses were superior to those with PBMC, and isolated B cells failed to present allergoids. Considerable IL-12 production was observed only when using the DC for Ag presentation of both allergens and allergoids. The amount of IL-10 in supernatants was dependent on the phenotype of the respective T cell clone. High IL-10 production was associated with suppressed IL-12 production from the DC in most cases. In conclusion, the reactivity of Th cells with allergoids is dependent on the type of the APC.

  2. Adjuvant effects of aluminium hydroxide-adsorbed allergens and allergoids - differences in vivo and in vitro.

    Science.gov (United States)

    Heydenreich, B; Bellinghausen, I; Lund, L; Henmar, H; Lund, G; Adler Würtzen, P; Saloga, J

    2014-06-01

    Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde- or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4(+) T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo. © 2014 British Society for Immunology.

  3. Molecular fingerprinting of complex grass allergoids: size assessments reveal new insights in epitope repertoires and functional capacities.

    Science.gov (United States)

    Starchenka, S; Bell, A J; Mwange, J; Skinner, M A; Heath, M D

    2017-01-01

    Subcutaneous allergen immunotherapy (SCIT) is a well-documented treatment for allergic disease which involves injections of native allergen or modified (allergoid) extracts. The use of allergoid vaccines is a growing sector of the allergy immunotherapy market, associated with shorter-course therapy. The aim of this study was the structural and immunological characterisation of group 1 (Lol p 1) IgG-binding epitopes within a complex mix grass allergoid formulation containing rye grass. HP-SEC was used to resolve a mix grass allergoid preparation of high molecular weight into several distinct fractions with defined molecular weight and elution profiles. Allergen verification of the HP-SEC allergoid fractions was confirmed by mass spectrometry analysis. IgE and IgG immunoreactivity of the allergoid preparations was explored and Lol p 1 specific IgG-binding epitopes mapped by SPOT synthesis technology (PepSpot™) with structural analysis based on a Lol p 1 homology model. Grass specific IgE reactivity of the mix grass modified extract (allergoid) was diminished in comparison with the mix grass native extract. A difference in IgG profiles was observed between an intact mix grass allergoid preparation and HP-SEC allergoid fractions, which indicated enhancement of accessible reactive IgG epitopes across size distribution profiles of the mix grass allergoid formulation. Detailed analysis of the epitope specificity showed retention of six Lol p 1 IgG-binding epitopes in the mix grass modified extract. The structural and immunological changes which take place following the grass allergen modification process was further unravelled revealing distinct IgG immunological profiles. All epitopes were mapped on the solvent exposed area of Lol p 1 homology model accessible for IgG binding. One of the epitopes was identified as an 'immunodominant' Lol p 1 IgG-binding epitope (62-IFKDGRGCGSCFEIK-76) and classified as a novel epitope. The results from this study support the concept

  4. Immunotherapy: what lies beyond.

    Science.gov (United States)

    Casale, Thomas B; Stokes, Jeffrey R

    2014-03-01

    Allergen immunotherapy has been used to treat allergic diseases, such as asthma, allergic rhinitis, and venom allergy, since first described over a century ago. The current standard of care in the United States involves subcutaneous administration of clinically relevant allergens for several months, building up to eventual monthly injections for typically 3 to 5 years. Recent advances have improved the safety and efficacy of immunotherapy. The addition of omalizumab or Toll-like receptor agonists to standard subcutaneous immunotherapy has proved beneficial. Altering the extract itself, either through chemical manipulation producing allergoids or directly producing recombinant proteins or significant peptides, has been evaluated with promising results. The use of different administration techniques, such as sublingual immunotherapy, is common in Europe and is on the immediate horizon in the United States. Other methods of administering allergen immunotherapy have been studied, including epicutaneous, intralymphatic, intranasal, and oral immunotherapy. In this review we focus on new types and routes of immunotherapy, exploring recent human clinical trial data. The promise of better immunotherapies appears closer than ever before, but much work is still needed to develop novel immunotherapies that induce immunologic tolerance and enhanced clinical efficacy and safety over that noted for subcutaneous allergen immunotherapy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  5. The Impact on Allergy-Related Cells of a Birch Pollen Allergoid, with and without Monophosphoryl Lipid A, in Comparison with the Native Equivalent.

    Science.gov (United States)

    Worm, Margitta; Ernst, Dennis; Kraller, Markus; Babina, Magda

    2017-01-01

    The clinical efficacy and safety of allergoid immunotherapy have been demonstrated in clinical trials. However, simultaneous monitoring of the immunological changes by allergoids versus allergens in the cells of the same individual has not been extensively performed, and the impact of concurrent Toll-like receptor 4 (TLR4) ligation has not been specified. Three types of birch allergen were utilized: glutaraldehyde-treated allergoid (extract A), the same allergoid plus monophosphoryl lipid A (MPL), i.e., TLR4 ligand (extract A*), and native allergen (extract B). Antigen-specific responses after the in vitro stimulation of blood cells with the extracts were assessed by studying costimulatory receptors on the B cell surface by flow cytometry, cytokine responses by ELISA, and CD63 and CD203c upregulation (basophil activation test) in allergic versus nonallergic subjects. HLA-DR selectively increased upon allergen or allergoid treatment in the allergic group only. The extract types elicited similar cytokine responses, with IL-6 and IL-10 production detected only in certain atopic subjects. The allergoids revealed a strong reduction (100- to allergoid employed was sharply reduced when compared to the native allergen, while its immunogenicity was largely retained, especially in the presence of MPL. We also provide further evidence that allergic and nonallergic individuals show preexisting differences in their immune repertoires. © 2017 S. Karger AG, Basel.

  6. Responses of human birch pollen allergen-reactive T cells to chemically modified allergens (allergoids).

    Science.gov (United States)

    Dormann, D; Ebner, C; Jarman, E R; Montermann, E; Kraft, D; Reske-Kunz, A B

    1998-11-01

    Allergoids are widely used in specific immunotherapy for the treatment of IgE-mediated allergic diseases. The aim of this study was to analyse whether a modification of birch pollen allergens with formaldehyde affects the availability of T-cell epitopes. Efficient modification of the allergens was verified by determining IgE and IgG binding activity using ELISA inhibition tests. T-cell responses to birch pollen allergoids were analysed in polyclonal systems, using peripheral blood mononuclear cells (PBMC) of five birch pollen-allergic individuals, as well as birch pollen extract-reactive T-cell lines (TCL), established from the peripheral blood of 14 birch pollen-allergic donors. To determine whether the modification of natural (n)Bet v 1 with formaldehyde or maleic anhydride results in epitope-specific changes in T-cell reactivities, 22 Bet v 1-specific T-cell clones (TCC), established from nine additional birch pollen-allergic individuals, were tested for their reactivity with these products. The majority of PBMC and TCL showed a reduced response to the birch pollen extract allergoid. Bet v 1-specific TCC could be divided into allergoid-reactive and -non-reactive TCC. No simple correlation between possible modification sites of formaldehyde in the respective T-cell epitopes and the stimulatory potential of the allergoid was observed. Mechanisms of suppression or of anergy induction were excluded as an explanation for the non-reactivity of representative TCC. All TCC could be stimulated by maleylated and unmodified nBet v 1 to a similar extent. These results demonstrate differences in the availability of T-cell epitopes between allergoids and unmodified allergens, which are most likely due to structural changes within the allergen molecule.

  7. Physicochemical and immunologic characterization of low-molecular-weight allergoids of Dactylis glomerata pollen proteins.

    Science.gov (United States)

    Cirković, T D; Bukilica, M N; Gavrović, M D; Vujcić, Z M; Petrović, S; Jankov, R M

    1999-02-01

    Orchard grass (Dactylis glomerata) pollen proteins were chemically modified by means of acid anhydrides (maleic and succinic anhydride) to obtain low-molecular-weight allergoids. Chemical modification in both cases led to the replacement of one positive charge (epsilon amino group of Lys) by one negative charge, yielding proteins with changed physicochemical properties in comparison to the native orchard grass-pollen proteins. Physicochemical characterization of derivatives was done by gel chromatography, SDS-PAGE, and isoelectric focusing. To examine the IgE-binding properties of these derivatives, we carried out immunoblotting. To examine the ability of derivatives to induce IgG production, we immunized rabbits. Skin prick testing with the allergoids was performed on 15 individuals allergic to orchard grass pollens and on two healthy subjects. It was shown that the modified proteins retain their original molecular weights, but change pI to more acidic values. In the case of allergoids, a strong reduction in IgE binding was found. Immunization of rabbits with allergoids showed that the derivatives retain the ability to induce IgG production, and that the antisera obtained in such a way react to native (unmodified) extract. The ability of derivatives to induce allergic reaction was significantly reduced. The patients (86.6%) included in our study exhibited less than 50% of native extract response. Among them, 53.3% had no response to one or both allergoids. These modification procedures yield allergoids with a reduced allergenic activity and preserved immunogenic potential suitable for use in immunotherapy.

  8. Adjuvant effects of aluminium hydroxide-adsorbed allergens and allergoids – differences in vivo and in vitro

    Science.gov (United States)

    Heydenreich, B; Bellinghausen, I; Lund, L; Henmar, H; Lund, G; Adler Würtzen, P; Saloga, J

    2014-01-01

    Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde-or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4+ T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo. PMID:24528247

  9. [A comparative immunochemical analysis of allergoids and allergens].

    Science.gov (United States)

    Fradkin, V A; Tsvetkov, N V; Diakiv, V V; Lavrenchik, E I

    1992-01-01

    In comparison with allergens having protein fragments with a molecular weight not exceeding 110 kD, allergoids have been found to consist of larger fragments with a molecular weight of 10-150 kD. Allergoids have less charged components than initial allergens and less antigenic components. Allergoids retain their capacity for stimulating the production of antibodies, specific to all antigenic components.

  10. Localized CD47 blockade enhances immunotherapy for murine melanoma.

    Science.gov (United States)

    Ingram, Jessica R; Blomberg, Olga S; Sockolosky, Jonathan T; Ali, Lestat; Schmidt, Florian I; Pishesha, Novalia; Espinosa, Camilo; Dougan, Stephanie K; Garcia, K Christopher; Ploegh, Hidde L; Dougan, Michael

    2017-09-19

    CD47 is an antiphagocytic ligand broadly expressed on normal and malignant tissues that delivers an inhibitory signal through the receptor signal regulatory protein alpha (SIRPα). Inhibitors of the CD47-SIRPα interaction improve antitumor antibody responses by enhancing antibody-dependent cellular phagocytosis (ADCP) in xenograft models. Endogenous expression of CD47 on a variety of cell types, including erythrocytes, creates a formidable antigen sink that may limit the efficacy of CD47-targeting therapies. We generated a nanobody, A4, that blocks the CD47-SIRPα interaction. A4 synergizes with anti-PD-L1, but not anti-CTLA4, therapy in the syngeneic B16F10 melanoma model. Neither increased dosing nor half-life extension by fusion of A4 to IgG2a Fc (A4Fc) overcame the issue of an antigen sink or, in the case of A4Fc, systemic toxicity. Generation of a B16F10 cell line that secretes the A4 nanobody showed that an enhanced response to several immune therapies requires near-complete blockade of CD47 in the tumor microenvironment. Thus, strategies to localize CD47 blockade to tumors may be particularly valuable for immune therapy.

  11. Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies

    OpenAIRE

    L?pez-Matas, M. Angeles; Gallego, Mayte; Iraola, V?ctor; Robinson, Douglas; Carn?s, Jer?nimo

    2013-01-01

    Background. The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT) has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol) allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Methods. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtain...

  12. In vitro evidence of efficacy and safety of a polymerized cat dander extract for allergen immunotherapy.

    Science.gov (United States)

    Morales, María; Gallego, Mayte; Iraola, Victor; Taulés, Marta; de Oliveira, Eliandre; Moya, Raquel; Carnés, Jerónimo

    2017-02-24

    Allergy to cat epithelia is highly prevalent, being the major recommendation for allergy sufferers its avoidance. However, this is not always feasible. Allergen specific immunotherapy is therefore recommended for these patients. The use of polymerized allergen extracts, allergoids, would allow to achieve the high allergen doses suggested to be effective while maintaining safety. Cat native extract and its depigmented allergoid were manufactured and biochemically and immunochemically characterized. Protein and chromatographic profiles showed significant modification of the depigmented allergoid with respect to its corresponding native extract. However, the presence of different allergens (Fel d 1, Fel d 2, Fel d 3, Fel d 4 and Fel d 7) was confirmed in the allergoid. Differences in IgE-binding capacity were observed as loss of biological potency and lower stability of the IgE-allergen complex on surface plasmon resonance. The allergoid induced production of IgG antibodies able to block IgE-binding to native extract. Finally, studies carried out with peripheral-blood mononuclear cells from cat allergic patients showed that the allergoid induced IFN-γ and IL-10 production similar to that induced by native extract. Cat depigmented allergoid induced production of cytokines involved in a Th1 and Treg response, was able to induce production of IgG-antibodies that blocks IgE-binding to cat native extract, and showed reduced interaction with IgE, suggesting greater safety than native extract while maintaining in vitro efficacy.

  13. Ultrarush schedule of subcutaneous immunotherapy with modified allergen extracts is safe in paediatric age.

    Science.gov (United States)

    Morais-Almeida, Mário; Arêde, Cristina; Sampaio, Graça; Borrego, Luis Miguel

    2016-01-01

    Traditional subcutaneous immunotherapy up dosing with allergenic extracts has been shown to be associated with frequent adverse reactions. In recent studies it has been demonstrated that using modified extracts, namely allergoids, it is a safe and effective procedure particularly on accelerated schedules. However data assessing its safety in paediatric age is scarce. To evaluate the safety profile in paediatric population of using modified allergen extracts, in an ultrarush schedule, to reach the maintenance dose in the first day. We included children undergoing treatment with subcutaneous immunotherapy during a five-year period, using modified aeroallergen extracts, depigmented, polymerized with glutaraldehyde and adsorbed on aluminium hydroxide using an ultrarush induction phase. The type of adverse reactions during the ultrarush protocol was recorded. We studied 100 paediatric patients (57 males) with a mean age of 11.6 years (5 to 18 years; standard deviation, 3.3), all with moderate to severe persistent rhinitis, with or without allergic conjunctivitis, asthma and atopic eczema, sensitized to mites and/or pollens. All reached the maintenance dose of 0.5 mL in the first day, except 1 child. During the ultrarush protocol the total number of injections was 199. There were 21 local adverse reactions in 11 patients, 11 immediate and 10 delayed; from those, had clinical relevance 1 immediate and 4 delayed. Systemic reactions were recorded in 2 cases, both immediate and mild. The ultrarush protocol, without premedication, was a safe alternative to be used in paediatric age during the induction phase of subcutaneous immunotherapy using allergoid depigmented extracts.

  14. Effect of Local Nasal Immunotherapy on Nasal Blockage in Pollen-Induced Allergic Rhinitis of Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Takeshi Nabe

    2008-01-01

    Conclusions: Local nasal immunotherapy may be clinically useful for allergic nasal blockage associated with nasal hyperresponsiveness. The mechanisms responsible for this effectiveness might not be related to IgE production. Additionally, the effectiveness for nasal tissue was dissociated from that seen for the ocular tissue.

  15. Characterization of allergoids from ovalbumin in vitro and in vivo.

    Science.gov (United States)

    Salgado, J; Casadevall, G; Puigneró, V; Queralt, J

    1996-01-01

    Several in vivo and in vitro methods for monitoring immunological properties of two allergoids obtained by formaldehyde treatment of ovalbumin (OA) were developed. The calculated molecular weight of allergoids was 80 kD (OA-F1) and 165 kD (OA-F2), respectively. The allergenic activity in vitro of allergoids in mast-cell histamine release assay was 1000 times lower than of OA. Both allergoids showed reduced ability to induce passive cutaneous anaphylaxis in the Sprague-Dawley rats or systemic anaphylaxis in Dunkin-Harley guinea-pigs. The ability of OA and allergoids to bind to the OA-specific IgE antibodies was measured in vivo by the inhibition of passive cutaneous anaphylaxis (PCA-inhibition). Allergoid binding to IgE was 51-66% lower than the native allergen. Moreover, the avidity of OA-specific IgG antibodies, measured by ELISA-inhibition, for allergoids and allergen was of the same order. Allergoids induced a different pattern of humoral immune response from that, induced by the native allergen. Thus, after immunization of BALB/c mouse, both allergoids induced a higher production of IgG and a lower production of IgE than OA, only OA-F2 induced a lower production of IgG1. The differences in the IgA response to the immunogens was not significant. Delayed hypersensitivity studies in the BALB/c mouse showed that allergoids were 5- to 12-times less effective in inducing a cell-mediated immune response than OA. The present study provides a battery of immunological methods for preclinical testing of modified allergens.

  16. Towards evidence-based medicine in specific grass pollen immunotherapy.

    Science.gov (United States)

    Calderon, M; Mösges, R; Hellmich, M; Demoly, P

    2010-04-01

    When initiating grass pollen immunotherapy for seasonal allergic rhinoconjunctivitis, specialist physicians in many European countries must choose between modalities of differing pharmaceutical and regulatory status. We applied an evidence-based medicine (EBM) approach to commercially available subcutaneous and sublingual Gramineae grass pollen immunotherapies (SCIT and SLIT) by evaluating study design, populations, pollen seasons, treatment doses and durations, efficacy, quality of life, safety and compliance. After searching MEDLINE, Embase and the Cochrane Library up until January 2009, we identified 33 randomized, double-blind, placebo-controlled trials (including seven paediatric trials) with a total of 440 specific immunotherapy (SIT)-treated subjects in seven trials (0 paediatric) for SCIT with natural pollen extracts, 168 in three trials (0 paediatric) for SCIT with allergoids, 906 in 16 trials (five paediatric) for natural extract SLIT drops, 41 in two trials (one paediatric) for allergoid SLIT tablets and 1605 in five trials (two paediatric) for natural extract SLIT tablets. Trial design and quality varied significantly within and between SIT modalities. The multinational, rigorous trials of natural extract SLIT tablets correspond to a high level of evidence in adult and paediatric populations. The limited amount of published data on allergoids prevented us from judging the level of evidence for this modality.

  17. Open-label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients

    NARCIS (Netherlands)

    Rieker-Schwienbacher, Juliane; Nell, Marja J.; Diamant, Zuzana; van Ree, Ronald; Distler, Andreas; Boot, Johan D.; Kleine-Tebbe, Jörg

    2013-01-01

    BACKGROUND: The current maintenance dose (10,000 AUeq/monthly) of a subcutaneous allergoid for house dust mite (HDM) immunotherapy has previously shown significant clinical efficacy in patients with HDM induced allergic rhinitis or rhinoconjunctivitis. In order to comply with the 2009 EMA guidelines

  18. Medication persistence with long-term, specific grass pollen immunotherapy measured by prescription renewal rates.

    Science.gov (United States)

    Sieber, J; De Geest, S; Shah-Hosseini, K; Mösges, R

    2011-04-01

    We assessed medication persistence using prescription renewal rates for grass pollen specific immunotherapy (SIT) in a representative population of patients in Germany to evaluate whether the perception of superior persistence for the subcutaneous route compared to the sublingual route could be confirmed in clinical practice. Individual prescriptions for allergen immunotherapy were extracted from a national prescription database (INSIGHT Health) and followed over 3 years on a per-patient basis. However, patients' medical history and treatment schedules were not available for analysis. Products were identified by the national drug code (PZN number) and grouped to either subcutaneous immunotherapy (SCIT) with natural extract injections, SCIT with modified allergens (allergoids) or sublingual immunotherapy (SLIT) with natural pollen extract solutions. Persistence was defined as at least one prescription of the individual drug in the respective years. A total of 1409 patients started SIT in 2005 (112, 695, and 602 for natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively). In 2006, 71%, 55%, and 59% of those patients had at least one renewal prescription of natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively, as well as 51%, 34%, and 39% in 2007. In both years, persistence with natural extract SLIT was significantly higher than with natural extract SCIT (p = 0.0015 for 2006, p = 0.0003 for 2007) and allergoid SCIT (p = 0.0152 for 2006, p = 0.0111 for 2007). There were no significant differences between the two SCIT groups. Medication persistence with grass pollen SIT in a representative sample of patients in Germany was similar to published medication persistence in asthma and COPD patients. The sublingual application route shows significantly better persistency than the subcutaneous route with native allergens or allergoids.

  19. The influence of a residual group in low-molecular-weight allergoids of Artemisia vulgaris pollen on their allergenicity, IgE- and IgG-binding properties.

    Science.gov (United States)

    Cirković, T; Gavrović-Jankulović, M; Prisić, S; Jankov, R M; Burazer, L; Vucković, O; Sporcić, Z; Paranos, S

    2002-11-01

    Reaction of epsilon-amino groups of lysine with potassium cyanate, maleic, or succinic anhydride leads to allergoids of low molecular weight. No study has been performed to compare their properties and investigate the influence of a residual group on allergenicity and human IgE- and IgG-binding of these derivatives. Allergoids of a pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, and succinic and maleic anhydride. Biochemical properties were investigated by determination of amino groups, enzyme activity, isoelectric focusing IEF and SDS-PAGE. IgE- and IgG-binding was determined using immunoblots and ELISA inhibition. Allergenicity was investigated by skin prick tests (SPT) on a group of 52 patients, of which 6 were control subjects, 30 were patients with no previous immunotherapy (IT), and 16 were patients undergoing immunotherapy. The same degree of amino-group modification (more than 85%), residual enzyme activity (less then 15%), IEF, and SDS-PAGE pattern were noted. In the immunoblots of IgE-binding, there was more pronounced reduction in the succinyl and maleyl derivatives than in the carbamyl one. IgG-binding was less affected by carbamylation than by acid anhydride modification. The SPT showed that the succinylated derivative had the most reduced allergenicity (98% showed a reduced wheal diameter when tested with the succinyl derivative, 87% with the maleyl allergoid, and 83% with the carbamyl allergoid). The most significant difference among allergoids could be seen in the group of patients with high skin reactivity (83% of patients showed no reaction to the succinyl derivative when compared to the value of 28% for the carbamyl derivative or 22% for the maleyl derivative). According to our results, all three modification procedures yielded allergoids with a similar extent of modification. No single biochemical parameter investigated in the study could predict the degree of reduced allergenicity in vivo. The most reduced

  20. Modified Allergens for Immunotherapy.

    Science.gov (United States)

    Satitsuksanoa, Pattraporn; Głobińska, Anna; Jansen, Kirstin; van de Veen, Willem; Akdis, Mübeccel

    2018-02-16

    During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT. In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens. The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.

  1. Sublingual Immunotherapy: Recent Advances

    Directory of Open Access Journals (Sweden)

    Enrico Compalati

    2013-01-01

    Full Text Available The practice of administering sublingual immunotherapy for respiratory allergy is gaining more and more diffusion worldwide as a consequence of the robust demonstration of clinical efficacy and safety provided by recent high-powered and well-designed studies, confirming for individual seasonal allergens the results of previous metanalyses in adult and pediatric populations. Preliminary evidence derives from recent rigorous trials on perennial allergens, like house dust mites, and specifically designed studies addressed the benefits on asthma. Emerging research suggests that SLIT may have a future role in other allergic conditions such as atopic dermatitis, food, latex and venom allergy. Efforts to develop a safer and more effective SLIT for inhalant allergens have led to the development of allergoids, recombinant allergens and formulations with adjuvants and substances targeting antigens to dendritic cells that possess a crucial role in initiating immune responses. The high degree of variation in the evaluation of clinical effects and immunological changes requires further studies to identify the candidate patients to SLIT and biomarkers of short and long term efficacy. Appropriate management strategies are urgently needed to overcome the barriers to SLIT compliance.

  2. Cancer Immunotherapy

    Science.gov (United States)

    Immunotherapy is a cancer treatment that helps your immune system fight cancer. It is a type of biological therapy. Biological therapy uses substances ... t yet use immunotherapy as often as other cancer treatments, such as surgery, chemotherapy, and radiation therapy. ...

  3. A 12-week DBPC dose-finding study with sublingual monomeric allergoid tablets in house dust mite-allergic patients.

    Science.gov (United States)

    Hüser, C; Dieterich, P; Singh, J; Shah-Hosseini, K; Allekotte, S; Lehmacher, W; Compalati, E; Mösges, R

    2017-01-01

    In sublingual immunotherapy, optimal doses are a key factor for therapeutic outcomes. The aim of this study with tablets containing carbamylated monomeric house dust mite allergoids was to determine the most effective and safe dose. In this double-blind, placebo-controlled dose-finding study, 131 patients with house dust mite-induced allergic rhinoconjunctivitis were randomized to 12-week treatments with 300 UA/day, 1000 UA/day, 2000 UA/day, 3000 UA/day or placebo. Conjunctival provocation tests (CPT) were performed before, during and after treatment. The change in mean allergic severity (primary endpoint), calculated from the severity of the CPT reaction, and the proportion of patients with an improved CPT threshold (secondary endpoint) determined the treatment effect. The mean allergic severity decreased in all groups, including the placebo group. It was lower in all active treatment groups (300 UA/day: 0.14, 1000 UA/day: 0.15, 2000 UA/day: 0.10, 3000 UA/day: 0.15) than in the placebo group (0.30). However, this difference was not statistically significant (P allergoid sublingual tablets is well tolerated and reduces the CPT reaction in house dust mite-allergic patients. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

  4. Safety of ultrashort-term sit with pollen allergoids adjuvanted by monophosphoryl lipid A: a prospective Italian survey.

    Science.gov (United States)

    Crivellaro, M; Senna, G E; Pappacoda, A; Vanzelli, R; Spacal, B; Marchi, G; Recchia, G; Makatsori, M

    2011-03-01

    A 3-year prospective post marketing survey on the safety of the recently developed ultrashort pre-seasonal subcutaneous immunotherapy (uSCIT-MPL4) with pollen allergoids adjuvanted with monophosphoryl lipid A was performed. A total of 510 patients received uSCIT-MPL4, 61% for grass, 35.7% for birch, 13.2% for parietaria and 3% for other pollens (ragweed, mugwort, and olive). A total of 3308 injections were given and the mean duration of uSCIT-MPL-4 was 2.3 years. Overall, only 7 slight systemic reactions (SR) were observed in 510 patients (1.37%) and 2.11/1000 injections suggesting that this treatment is even safer than traditional depot injection SIT.

  5. Measurement of basophil-activating capacity of grass pollen allergens, allergoids and hypoallergenic recombinant derivatives by flow cytometry using anti-CD203c.

    Science.gov (United States)

    Kahlert, H; Cromwell, O; Fiebig, H

    2003-09-01

    The assessment of the basophil-activating potential is an important aspect in the development of improved preparations for specific immunotherapy. The aim of the study was to evaluate the suitability of CD203c expression as a measure of basophil activation to compare allergoids with original allergen extracts, and recombinant hypoallergenic allergen derivatives with recombinant wild-type and natural allergens. Heparinized whole blood samples from grass pollen allergic subjects were stimulated with grass pollen allergens and allergen derivatives followed by labelling of the basophils with PE-conjugated anti-CD203c. After lysis of the erythrocytes and fixation, the basophils were detected by flow cytometry. In some experiments, histamine release was determined simultaneously. Grass pollen allergoids revealed a 10-10 000-fold reduction of basophil-activating capacity measured by CD203c expression. The deletion mutant DM4 of rPhl p 5b showed stronger hypoallergenic characteristics in a range of 50-10 000-fold reduction, whereas a combination mutant of rPhl p 5b and Phl p 6 revealed less hypoallergenic features. Histamine release experiments led to a similar outcome as CD203c measurement. The measurement of CD203c expression on basophils by flow cytometry provides a rapid and sensitive method for the estimation of the allergic or hypoallergenic features of allergen preparations. The results demonstrated the hypoallergenicity of grass pollen allergoids and of the rPhl p 5b variant DM4, which may be a candidate in future preparations for specific immunotherapy.

  6. Studies on `allergoids' prepared from naturally occurring allergens

    Science.gov (United States)

    Marsh, D. G.; Lichtenstein, L. M.; Campbell, D. H.

    1970-01-01

    The highly purified major allergenic component of rye grass pollen (Group I) was used to investigate the possibility of destroying selectively the allergenic properties of an antigen, while largely retaining its original immunizing capacities. The allergen was treated under mild conditions with formalin alone or formalin plus a reactive low molecular weight additive. Certain derivatives (allergoids) showed well over 99 per cent reduction in allergenicity, determined by the histamine released from allergic human leucocytes in vitro, but were still able to combine with rabbit antibody against native antigen. Furthermore, the allergoids stimulated production (in guinea-pigs) of appreciable amounts of antibody able to inhibit native allergen-mediated human allergic histamine release in vitro and to cross-react with native antigen by PCA tests in normal guinea-pigs. Residual allergenicity and cross-immunogenicity (by the inhibition assay) of the different formalinized derivatives varied appreciably according to the additive used in formalinization, but the cross-reactivities of the different preparations in quantitative precipitin analysis against rabbit anti-native antigen serum were similar. The residual allergenicities of individual derivatives varied by up to 1000-fold in different cell preparations, suggesting a heterogeneity of allergenic determinants. Allergoid derivatives showed no hapten-like activity in that they were unable to inhibit allergen-mediated histamine release from leucocytes. The theoretical and practical application of allergoids is discussed, including their potential usefulness in improving the immunotheraphy of atopic humans. ImagesFIG. 2 PMID:4192674

  7. 98 Specific IGE and IGG Binding to Allergoids of Phleum pratense

    OpenAIRE

    Cases, Barbara; Fernandez-Caldas, Enrique; Tudela, Jose Ignacio; Fernandez, Eva Abel; Sanchez-Garcia, Silvia; Ibañez, M. Dolores; Escudero, Carmelo; Casanovas, Miguel

    2012-01-01

    Background Allergoids were first used in the decades of the 60s and 70s of the last century as an effective treatment of allergic respiratory diseases. Allergoids can be modified with formaldehyde or glutaraldehyde. Modified allergens, or allergoids, decrease the risk of adverse reactions while administering higher allergen doses. The objective of this study was to analyse specific IgE and IgG binding to glutaraldehyde modified and non-modified allergen extracts of Phleum pratense. Methods Th...

  8. Immunotherapy (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Immunotherapy KidsHealth / For Parents / Immunotherapy What's in this article? ... Types of Immunotherapy Side Effects Outlook Print About Immunotherapy Immunotherapy, also known as targeted therapy or biotherapy, ...

  9. Depigmented allergoids reveal new epitopes with capacity to induce IgG blocking antibodies.

    Science.gov (United States)

    López-Matas, M Angeles; Gallego, Mayte; Iraola, Víctor; Robinson, Douglas; Carnés, Jerónimo

    2013-01-01

    The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT) has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol) allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. Depigmented-polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG-antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT.

  10. Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients.

    Science.gov (United States)

    Mösges, Ralph; Rohdenburg, Christina; Eichel, Andrea; Zadoyan, Gregor; Kasche, Elena-Manja; Shah-Hosseini, Kija; Lehmacher, Walter; Schmalz, Petra; Compalati, Enrico

    2017-11-01

    To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. This study found 1000 UA/day to be the optimal effective and safe dose.

  11. Fractionation and immunological characterization of allergens and allergoids of Prosopis juliflora pollen.

    Science.gov (United States)

    Thakur, I S; Kamal; Mishra, S

    1991-06-01

    Allergoids of Prosopis juliflora pollen were prepared by formalinization of crude allergen and glycoprotein. Fractionation of crude allergen and allergoids on Sephadex G-100 resulted in separation of proteins of varying molecular size and a glycoprotein of 81 to 13 KD. Allergoids prepared from the glycoprotein fractionated into two proteins of approximately 200 KD and more than 200 KD. Crossed immunoelectrophoresis indicated 12 and gel diffusion test 3 precipitating antigens incrude allergen extract; by these tests allergoids depicted 8 and 3 precipitin bands, respectively. The precipitin analysis showed heterogeneity of allergenic determinants and also variation in cross-immunogenicity of the formalinized derivatives. The skin prick and radioallergosorbent tests depicted greater activity of fractionated crude allergens than the allergoids. The above tests suggest altered and concealed antigenic determinants as result of formalinization of P. juliflora pollen which, however, showed reduced allergenic activity relative to the native allergen.

  12. Cancer immunotherapy

    DEFF Research Database (Denmark)

    Cairns, Linda; Aspeslagh, Sandrine; Anichini, Andrea

    2016-01-01

    This report covers the Immunotherapy sessions of the 2016 Organisation of European Cancer Institutes (OECI) Oncology Days meeting, which was held on 15th-17th June 2016 in Brussels, Belgium. Immunotherapy is a potential cancer treatment that uses an individual's immune system to fight the tumour....... In recent years significant advances have been made in this field in the treatment of several advanced cancers. Cancer immunotherapies include monoclonal antibodies that are designed to attack a very specific part of the cancer cell and immune checkpoint inhibitors which are molecules that stimulate...... or block the inhibition of the immune system. Other cancer immunotherapies include vaccines and T cell infusions. This report will summarise some of the research that is going on in this field and will give us an update on where we are at present....

  13. Novel vaccines targeting dendritic cells by coupling allergoids to nonoxidized mannan enhance allergen uptake and induce functional regulatory T cells through programmed death ligand 1.

    Science.gov (United States)

    Sirvent, Sofía; Soria, Irene; Cirauqui, Cristina; Cases, Bárbara; Manzano, Ana I; Diez-Rivero, Carmen M; Reche, Pedro A; López-Relaño, Juan; Martínez-Naves, Eduardo; Cañada, F Javier; Jiménez-Barbero, Jesús; Subiza, Javier; Casanovas, Miguel; Fernández-Caldas, Enrique; Subiza, José Luis; Palomares, Oscar

    2016-08-01

    Allergen immunotherapy (AIT) is the only curative treatment for allergy. AIT faces pitfalls related to efficacy, security, duration, and patient compliance. Novel vaccines overcoming such inconveniences are in demand. We sought to study the immunologic mechanisms of action for novel vaccines targeting dendritic cells (DCs) generated by coupling glutaraldehyde-polymerized grass pollen allergoids to nonoxidized mannan (PM) compared with glutaraldehyde-polymerized allergoids (P) or native grass pollen extracts (N). Skin prick tests and basophil activation tests with N, P, or PM were performed in patients with grass pollen allergy. IgE-blocking experiments, flow cytometry, confocal microscopy, cocultures, suppression assays, real-time quantitative PCR, ELISAs, and ELISpot assays were performed to assess allergen capture by human DCs and T-cell responses. BALB/c mice were immunized with PM, N, or P. Antibody levels, cytokine production by splenocytes, and splenic forkhead box P3 (FOXP3)(+) regulatory T (Treg) cells were quantified. Experiments with oxidized PM were also performed. PM displays in vivo hypoallergenicity, induces potent blocking antibodies, and is captured by human DCs much more efficiently than N or P by mechanisms depending on mannose receptor- and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-mediated internalization. PM endorses human DCs to generate functional FOXP3(+) Treg cells through programmed death ligand 1. Immunization of mice with PM induces a shift to nonallergic responses and increases the frequency of splenic FOXP3(+) Treg cells. Mild oxidation impairs these effects in human subjects and mice, demonstrating the essential role of preserving the carbohydrate structure of mannan. Allergoids conjugated to nonoxidized mannan represent suitable vaccines for AIT. Our findings might also be of the utmost relevance to development of therapeutic interventions in other immune tolerance-related diseases. Copyright

  14. Depigmented and polymerised house dust mite allergoid: allergen content, induction of IgG4 and clinical response.

    Science.gov (United States)

    Gallego, M T; Iraola, V; Himly, M; Robinson, D S; Badiola, C; García-Robaina, J C; Briza, P; Carnés, J

    2010-01-01

    Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study. Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double-blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients' sera using the CAP system and direct ELISA experiments. Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment. The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts. Copyright (c) 2010 S. Karger AG, Basel.

  15. Current insights in allergen immunotherapy.

    Science.gov (United States)

    Passalacqua, Giovanni; Bagnasco, Diego; Ferrando, Matteo; Heffler, Enrico; Puggioni, Francesca; Canonica, Giorgio Walter

    2018-02-01

    Allergen-specific immunotherapy (AIT) in its subcutaneous and sublingual forms is currently a well-established and experimentally supported treatment for respiratory allergy and hymenoptera venom allergy. There have been advances in its use linked strictly to the advancement in the knowledge of the molecular mechanisms of allergy, the production of well-characterized extracts, and diagnostic techniques. The use of AIT in asthma and the application of new approaches are expanding. We briefly review the advances and concerns in the use of AIT. PubMed and Scopus. The most recent and clinically relevant literature was selected and reviewed. The introduction of high-quality products supported by large dose-finding trials has yielded better defined indications, contraindications, and modalities of use. Some specific products in tablet form have recently been approved in the United States. Sublingual immunotherapy has been found to be effective in asthma, which until recently had been a matter of debate. Another promising therapy is oral and sublingual desensitization for food allergy, for which encouraging results have recently been reported. In the near future, other options will be available, including new routes of administration (intralymphatic and epicutaneous), allergoids, engineered allergens, and peptides. The use of component-resolved diagnosis techniques will further refine and target AIT prescriptions. This condensed and updated review shows that AIT remains a viable treatment option, especially after the introduction of standardized tablets for some allergens. Food allergy and new administration routes represent a promising expansion. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Detection of allergen composition and in vivo immunogenicity of depigmented allergoids of Betula alba.

    Science.gov (United States)

    Carnés, J; Himly, M; Gallego, M; Iraola, V; Robinson, D S; Fernández-Caldas, E; Briza, P

    2009-03-01

    Chemical modification of allergen vaccines to reduce IgE binding improves safety while maintaining clinical efficacy. However, this also complicates the characterization of allergoids using techniques as for native allergen extracts. The objective of this study was to analyse the molecular size of Betula alba depigmented allergoids, conservation of major allergens in the allergoids and in vivo antibody response to immunization. The molecular size of depigmented allergoids was evaluated by high performance-size exclusion chromatography and light scattering techniques. Protein composition was compared with native extracts by capillary liquid chromatography-tandem mass spectrometry based peptide mapping. Rabbits were immunized with depigmented allergoid of Betula pollen adsorbed onto aluminium hydroxide (Depigoid). IgG antibodies against individual allergens were determined by ELISA and immunoblot. Depigmented allergoids contained a range of high molecular weight particles, approximately 60% of which had a molecular weight of 1-3 MDa. Peptide sequencing confirmed the preservation of five isoforms of Bet v 1, as well as Bet v 2, Bet v 6 and Bet v 7. Sera from immunized rabbits showed high levels of specific IgG to rBet v 1.0101 and rBet v 2. The mean protein content was 544+/-106 microg per mg of freeze-dried material for depigmented allergoids and 434+/-71 for native extracts. They retain the capacity to induce specific IgG antibodies against individual allergens present in the native extract. These findings confirm the immunogenicity of depigmented allergoids and may explain why patients treated with these vaccines are protected against the native allergens. Analysis of molecular size and allergen content may be useful techniques for characterization and standardization of allergoid products.

  17. Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies

    Directory of Open Access Journals (Sweden)

    M. Angeles López-Matas

    2013-01-01

    Full Text Available Background. The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Methods. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. Results. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. Conclusions. Depigmented-polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG-antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT.

  18. Allergen immunotherapy in allergic rhinitis: current use and future trends.

    Science.gov (United States)

    Klimek, Ludger; Pfaar, Oliver; Bousquet, Jean; Senti, Gabriela; Kündig, Thomas

    2017-09-01

    Type-1 allergies are among the most chronic common diseases of humans. Allergen immunotherapy (AIT) is the only causative and disease-modifying treatment option besides allergen avoidance. Severe systemic adverse allergic reactions may be induced by every AIT treatment. Different approaches have been used to provide safer AIT preparations to lower or even totally overcome this risk. Areas covered: A structured literature recherche in Medline and Pubmed under inclusion of national and international guidelines and Cochrane meta-analyses has been performed aiming at reviewing clinical use of such approaches in AIT. New allergen preparations may include allergoids, recombinant allergens (recA) and modified recombinant allergens (recA) in subcutaneous as well as in mucosal immunotherapies (application e.g. using bronchial, nasal, oral and sublingual application) with sublingual being the established mucosal application route and new ways of application like intralymphatic and epicutaneous immunotherapy. Expert commentary: Immune-modifying agents like Virus-like particles and CpG-motifs, adjuvants like MPL and aluminum hydroxide are evaluated and found to increase and direct the immunological response toward immunological tolerance. New forms of allergen extracts can improve safety and efficacy of AIT and may change our way of performing allergen immunotherapy in the future.

  19. Studies on allergoids from naturally occurring allergens. III. Preparation of ragweed pollen allergoids by aldehyde modification in two steps.

    Science.gov (United States)

    Marsh, D G; Norman, P S; Roebber, M; Lichtenstein, L M

    1981-12-01

    We have devised a new process for modifying heat-labile allergens, which employs a sequential "two-step" incubation at temperatures of 10 degree C and 30 degree to 32 degree C. This process was found to produce effective ragweed "allergoids" with low allergenicity and good immunogenicity, which makes them useful for the therapy of allergic humans. Modification with formaldehyde produced derivatives ("formallergoids") that were about 10-fold less allergenic in allergic humans (as measured by leukocyte histamine-release assay), and similarly or more immunogenic in guinea pigs, than glutaraldehyde-modified allergens ("glutarallergoids"). Further analysis by RAST inhibition showed that a ragweed formallergoid was sixfold less reactive than a glutarallergoid with a pool of human IgE antibodies. However, the formallergoid had retained the ability to induce a wide array of antibodies against native ragweed antigens, since rabbit anti-formallergoid serum was able to recognize at least 12 different ragweed antigens, including AgE. Gel-filtration experiments showed that both the formallergoid and glutarallergoid materials contained polymers having apparent molecular weights distributed around 260,000 and 230,000 daltons, respectively (approximate range 30,000 to 900,000 daltons). Our studies provide the immunochemical basis for the use of these allergoids in the therapy of allergic humans.

  20. Sarcoma Immunotherapy

    International Nuclear Information System (INIS)

    Gouw, Launce G.; Jones, Kevin B.; Sharma, Sunil; Randall, R. Lor

    2011-01-01

    Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis

  1. Sarcoma Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gouw, Launce G., E-mail: launce.gouw@hsc.utah.edu [Departments of Oncology, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Jones, Kevin B. [Departments of Orthopaedic Surgery, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Sharma, Sunil [Departments of Oncology, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Randall, R. Lor [Departments of Orthopaedic Surgery, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States)

    2011-11-10

    Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis.

  2. 98 Specific IGE and IGG Binding to Allergoids of Phleum pratense

    Science.gov (United States)

    Cases, Barbara; Fernandez-Caldas, Enrique; Tudela, Jose Ignacio; Fernandez, Eva Abel; Sanchez-Garcia, Silvia; Ibañez, M. Dolores; Escudero, Carmelo; Casanovas, Miguel

    2012-01-01

    Background Allergoids were first used in the decades of the 60s and 70s of the last century as an effective treatment of allergic respiratory diseases. Allergoids can be modified with formaldehyde or glutaraldehyde. Modified allergens, or allergoids, decrease the risk of adverse reactions while administering higher allergen doses. The objective of this study was to analyse specific IgE and IgG binding to glutaraldehyde modified and non-modified allergen extracts of Phleum pratense. Methods The sera of 69 patients sensitized to P. pratense were tested. All these patients had signs and symptoms of rhinoconjunctivitis with, or without, asthma in May and June of 2011. All these patients had positive skin prick tests to a standardized extract of P. pratense, and other grass species. Most patients were also sensitized to olive pollen. Specific IgE and IgG binding were analysed by direct ELISA against P. pratense native (non-modified) and allergoid extracts. Relative potencies were evaluated through ELISA inhibition assays, and the protein composition of non-modified and allergoid samples was determined by Mass Spectrometry (MS/MS). Results Mean Specific IgE levels against the native extract was 16.68 ± 11.65 Units (U) and against the allergoid: 7.26 ± 8.24 U (P allergoid (P = 0.16; Mann-Whitney). Linear regression coefficients obtained between immunoglobulin reactivity against both extracts were: r2 = 0.51 for specific IgE and r2 = 0.83 for specific IgG. An important decrease in the allergenic activity, measured by inhibition ELISA, was clearly observed. The MS/MS assay revealed the presence of the mayor allergen, and some isoforms, in non-modified and allergoid extracts. Conclusions Results obtained demonstrate that the glutaraldehyde polymerization process induces an important decrease in specific IgE binding to allergoids of P. pratense while there are no significant differences in specific IgG binding. The allergenic composition of the P. pratense allergoid was

  3. [A comparative evaluation of the biological action of allergens and allergoids prepared from plant pollen by the double radial immunodiffusion method].

    Science.gov (United States)

    Lavrenchik, E I; Korytina, O L

    1989-09-01

    Antisera to allergens and allergoids prepared from timothy, orchard grass, birch and wormwood pollen have been obtained and used in the double radial immunodiffusion test. The preparations of the allergoid row have been found capable of inducing immune response in laboratory animals (rabbits). Both forms of pollen preparations, allergens and allergoids, have been shown to possess common antigenic determinants reacting with antibodies present in antisera to allergens and allergoids. The absence of identity in the ratio of manifestations of gel precipitation reactions for allergoid with respect to the initial forms of allergens of individual pollen preparation has been noted.

  4. Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice.

    Science.gov (United States)

    Soria, I; López-Relaño, J; Viñuela, M; Tudela, J-I; Angelina, A; Benito-Villalvilla, C; Díez-Rivero, C M; Cases, B; Manzano, A I; Fernández-Caldas, E; Casanovas, M; Palomares, O; Subiza, J L

    2018-04-01

    Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM-allergoids administered sublingually in comparison with native allergens. Three immunization protocols (4-8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells. A quick antibody response and higher IgG2a/IgE ratio were observed with PM-allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL-4 ratio with a quick IL-10 production by submandibular LN cells. An increase in CD4 + CD25 high FOXP3 + Treg cells was detected in LNs and spleen of mice treated with PM-allergoids. These allergoids were better captured than native allergens by antigen-presenting (CD45 + MHC-II + ) cells obtained from the sublingual mucosa, including DCs (CD11b + ) and macrophages (CD64 + ). Importantly, all the differential effects induced by PM-allergoids were abolished when using oxidized instead of nonoxidized PM-allergoids. Our results demonstrate for the first time that PM-allergoids administered through the sublingual route promote the generation of Th1 and FOXP3 + Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen-presenting cells. © 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.

  5. Novel strategies in immunotherapy for allergic diseases.

    Science.gov (United States)

    Rajakulendran, Mohana; Tham, Elizabeth Huiwen; Soh, Jian Yi; Van Bever, H P

    2018-04-01

    Conventional immunotherapy (IT) for optimal control of respiratory and food allergies has been fraught with concerns of efficacy, safety, and tolerability. The development of adjuvants to conventional IT has potentially increased the effectiveness and safety of allergen IT, which may translate into improved clinical outcomes and sustained unresponsiveness even after cessation of therapy. Novel strategies incorporating the successful use of adjuvants such as allergoids, immunostimulatory DNA sequences, monoclonal antibodies, carriers, recombinant proteins, and probiotics have now been described in clinical and murine studies. Future approaches may include fungal compounds, parasitic molecules, vitamin D, and traditional Chinese herbs. More robust comparative clinical trials are needed to evaluate the safety, clinical efficacy, and cost effectiveness of various adjuvants in order to determine ideal candidates in disease-specific and allergen-specific models. Other suggested approaches to further optimize outcomes of IT include early introduction of IT during an optimal window period. Alternative routes of administration of IT to optimize delivery and yet minimize potential side effects require further evaluation for safety and efficacy before they can be recommended.

  6. Immunotherapy of Genitourinary Malignancies

    Directory of Open Access Journals (Sweden)

    Teruo Inamoto

    2012-01-01

    Full Text Available Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies.

  7. Tyrosine kinase inhibition increases the cell surface localization of FLT3-ITD and enhances FLT3-directed immunotherapy of acute myeloid leukemia.

    Science.gov (United States)

    Reiter, K; Polzer, H; Krupka, C; Maiser, A; Vick, B; Rothenberg-Thurley, M; Metzeler, K H; Dörfel, D; Salih, H R; Jung, G; Nößner, E; Jeremias, I; Hiddemann, W; Leonhardt, H; Spiekermann, K; Subklewe, M; Greif, P A

    2018-02-01

    The fms-related tyrosine kinase 3 (FLT3) receptor has been extensively studied over the past two decades with regard to oncogenic alterations that do not only serve as prognostic markers but also as therapeutic targets in acute myeloid leukemia (AML). Internal tandem duplications (ITDs) became of special interest in this setting as they are associated with unfavorable prognosis. Because of sequence-dependent protein conformational changes FLT3-ITD tends to autophosphorylate and displays a constitutive intracellular localization. Here, we analyzed the effect of tyrosine kinase inhibitors (TKIs) on the localization of the FLT3 receptor and its mutants. TKI treatment increased the surface expression through upregulation of FLT3 and glycosylation of FLT3-ITD and FLT3-D835Y mutants. In T cell-mediated cytotoxicity (TCMC) assays, using a bispecific FLT3 × CD3 antibody construct, the combination with TKI treatment increased TCMC in the FLT3-ITD-positive AML cell lines MOLM-13 and MV4-11, patient-derived xenograft cells and primary patient samples. Our findings provide the basis for rational combination of TKI and FLT3-directed immunotherapy with potential benefit for FLT3-ITD-positive AML patients.

  8. Immunotherapy in multimodality treatment

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    Application of immunotherapy for treatment of oncologic patients is considered. Monoclonal antibodies (MCA) are used for immunotherapy both independently and as carriers of various toxins, chemopreparations and radioactive isotopes. It is shown that immunotherapy should be considered as one of additional methods of multimodulity treatment of patients with malignant tumors

  9. Depigmented-polymerised allergoids favour regulatory over effector T cells: enhancement by 1α, 25-dihydroxyvitamin D3.

    Science.gov (United States)

    Urry, Zoe L; Richards, David F; Black, Cheryl; Morales, Maria; Carnés, Jerónimo; Hawrylowicz, Catherine M; Robinson, Douglas S

    2014-05-29

    Allergen immunotherapy (SIT) is the only treatment for allergic disease capable of modifying disease long term. To reduce the risk of anaphylaxis from SIT, allergen-extracts have been modified by polymerisation with glutaraldehyde to reduce IgE binding. It is suggested that these allergoid extracts also have reduced T cell activity, which could compromise clinical efficacy. Effective SIT is thought to act through regulatory T cells (Tregs) rather than activation of effector T cells. There is no published data on the activity of modified extracts on Tregs. We compared the capacity of modified (depigmented-polymerised) versus unmodified (native) allergen extracts of grass pollen and house dust mite to stimulate proliferation/cytokine production and to modulate Treg/effector T cell frequency in cultures of peripheral blood mononuclear cells (PBMC), from volunteers sensitised to both allergens in vitro. Depigmented-polymerised allergen extracts stimulated less proliferation of PBMC, and reduced effector cell numbers after 7 days in culture than did native extracts. However, the frequency of Foxp3+ Tregs in cultures were similar to those seen with native extract so that ratios of regulatory to effector T cells were significantly increased in cultures stimulated with depigmented-polymerised extracts. Addition of 1α, 25-dihydroxyvitamin D3 further favoured Treg, and reduced effector cytokine production, but not interleukin-10. Depigmented-polymerised allergen extracts appear to favour Treg expansion over activation of effector T cells and this may relate to their demonstrated efficacy and safety in SIT. 1α, 25-dihydroxyvitamin D3 further reduces effector T cell activation by allergen extracts and may be a useful adjuvant for SIT.

  10. Immunogenicity of Phleum pratense depigmented allergoid vaccines: experimental study in rabbits.

    Science.gov (United States)

    Iraola, V; Gallego, M T; López-Matas, M A; Morales, M; Bel, I; García, N; Carnés, J

    2012-01-01

    Immunogenicity studies are based on accurate preclinical and clinical assessment of pharmaceutical products. The immunogenicity of modified allergen vaccines has not been fully elucidated, and the mechanisms involved are not well understood. Animal and human models have recently shown that depigmented allergoids induce specific immunoglobulin (Ig) G against individual allergens, thus supporting the clinical efficacy of these vaccines. The aim of this study was to investigate the production of specific IgG against individual antigens and their isoforms in rabbits injected with depigmented allergoid extracts of Phleum pratense pollen. Two New Zealand rabbits were immunized with depigmented-polymerized extracts adsorbed onto aluminum hydroxide (Depigoid) of P pratense. Rabbits were injected 3 times (35 microg Phl p 5). Specific IgG titers against native, depigmented, and depigmented-polymerized extracts and individual allergens (rPhl p 1 and rPhl p 5a) were analyzed by direct enzyme-linked immunosorbent assay. The capacity of these synthesized antibodies to recognize individual native and depigmented allergens and different isoforms was evaluated by immunoblot and 2-D analysis. All rabbits produced high titers of specific IgG against the 3 extracts. Rabbits injected with depigmented allergoids produced similar specific antibody titers against native, depigmented, and depigmented-polymerized extracts. Serum samples recognized individual allergens and their isoforms in the nonmodified extracts. Vaccines containing depigmented allergoid extracts of P pratense induce immunogenicity in vivo. The antibodies produced after injection of these extracts clearly recognized allergens and different isoforms in their native configuration.

  11. The future of immunotherapy for canine atopic dermatitis: a review.

    Science.gov (United States)

    DeBoer, Douglas J

    2017-02-01

    Allergen specific immunotherapy (ASIT) is a foundation treatment for canine atopic dermatitis (CAD), though few critical studies have documented its effectiveness as a disease-modifying treatment in dogs. The mechanisms by which ASIT works in dogs have not been elucidated, although they are likely to parallel those known for humans. Current ASIT approaches in CAD focus on either subcutaneous or sublingual administration. Greater knowledge of major allergens in dogs, ideal dosage regimes and details of allergen admixture are likely to lead to better efficacy in CAD. Evaluation of biomarkers for successful therapy may also be of benefit. Potentially important advances in human medicine, that have yet to be explored in dogs, include use of modified allergen preparations such as allergoids, recombinant major allergens or allergen peptides; modification with adjuvants; or packaging of the above in virus-like particles. Co-administration of immunomodulators such as CpG oligodeoxynucleotides or specific monoclonal antibodies might direct the immune response in the desired direction while calming the "cytokine storm" of active disease. Initial trials of alternative routes of administration such as intralymphatic immunotherapy have yielded exciting results in humans, and continuing study in dogs is underway. Progress in ASIT of human food allergy may provide clues that will assist with improved diagnosis and patient management of CAD. Importantly, further study must be undertaken to clarify the conditions under which ASIT is a valuable treatment modality for dogs. © 2017 ESVD and ACVD.

  12. Allergen immunotherapy in people, dogs, cats and horses - differences, similarities and research needs.

    Science.gov (United States)

    Mueller, R S; Jensen-Jarolim, E; Roth-Walter, F; Marti, E; Janda, J; Seida, A A; DeBoer, D

    2018-04-19

    In human patients with seasonal allergic rhinoconjunctivitis sensitized to grass pollen, the first successful allergen immunotherapy (AIT) was reported in 1911. Today, immunotherapy is an accepted treatment for allergic asthma, allergic rhinitis and hypersensitivities to insect venom. AIT is also used for atopic dermatitis and recently for food allergy. Subcutaneous, epicutaneous, intralymphatic, oral and sublingual protocols of AIT exist. In animals, most data are available in dogs where subcutaneous AIT is an accepted treatment for atopic dermatitis. Initiating a regulatory response and a production of "blocking" IgG antibodies with AIT are similar mechanisms in human beings and dogs with allergic diseases. Although subcutaneous immunotherapy is used for atopic dermatitis in cats, data for its efficacy is sparse. There is some evidence for successful treatment of feline asthma with AIT. In horses, most studies evaluate the effect of AIT on insect hypersensitivity with conflicting results though promising pilot studies have demonstrated the prophylaxis of insect hypersensitivity with recombinant antigens of biting midges (Culicoides spp.). Optimising AIT using allergoids, peptide immunotherapy, recombinant allergens and new adjuvants with the different administration types of allergen extracts hopefully will further improve compliance and efficacy of this proven treatment modality. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Juhua Zhou; Yin Zhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy,radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future.

  14. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    JuhuaZhou; YinZhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy, radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future. Cellular & Molecular Immunology.

  15. Molecular diagnosis and immunotherapy.

    Science.gov (United States)

    Sastre, Joaquín; Sastre-Ibañez, Marina

    2016-12-01

    To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy. As specific allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy. Molecular diagnosis, when used with other tools and patients' clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice.

  16. Veterinary Oncology Immunotherapies.

    Science.gov (United States)

    Bergman, Philip J

    2018-03-01

    The ideal cancer immunotherapy agent should be able to discriminate between cancer and normal cells, be potent enough to kill small or large numbers of tumor cells, and be able to prevent recurrence of the tumor. Tumor immunology and immunotherapy are among the most exciting and rapidly expanding fields; cancer immunotherapy is now recognized as a pillar of treatment alongside traditional modalities. This article highlights approaches that seem to hold particular promise in human clinical trials and many that have been tested in veterinary medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Immunoscintigraphy and immunotherapy 1988

    International Nuclear Information System (INIS)

    Baum, R.P.; Perkins, A.C.

    1988-01-01

    This review reports some of the main presentations from some of the major centres in Europe currently working in the field of immunoscintigraphy and immunotherapy. The meeting was organised into 5 sessions. (orig./TRV)

  18. Immunotherapy for infectious diseases

    National Research Council Canada - National Science Library

    Jacobson, Jeffrey M

    2002-01-01

    .... The review of the current state of anti-HIV immunotherapy covers HIV-specific passive and active immunization strategies, gene therapy, and host cell-targeted approaches for treating HIV infection...

  19. Immunotherapy for cancer

    Science.gov (United States)

    ... 2017. Accessed February 15, 2018. Pardoll D. Cancer immunology. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan ... D.A.M. Editorial team. Related MedlinePlus Health Topics Cancer Immunotherapy Browse the Encyclopedia A.D.A. ...

  20. Cancer immunotherapy in children

    Science.gov (United States)

    More often than not, cancer immunotherapies that work in adults are used in modified ways in children. Seldom are new therapies developed just for children, primarily because of the small number of pediatric patients relative to the adult cancer patient

  1. Immunotherapy for Cervical Cancer

    Science.gov (United States)

    In an early phase NCI clinical trial, two patients with metastatic cervical cancer had a complete disappearance of their tumors after receiving treatment with a form of immunotherapy called adoptive cell transfer.

  2. Immunotherapy for glioblastoma: playing chess, not checkers.

    Science.gov (United States)

    Jackson, Christopher M; Lim, Michael

    2018-04-24

    Patients with glioblastoma (GBM) exhibit a complex state of immune dysfunction involving multiple mechanisms of local, regional, and systemic immune suppression and tolerance. These pathways are now being identified and their relative contributions explored. Delineating how these pathways are interrelated is paramount to effectively implementing immunotherapy for GBM. Copyright ©2018, American Association for Cancer Research.

  3. Synthetic immune niches for cancer immunotherapy

    NARCIS (Netherlands)

    Weiden, J.; Tel, J.; Figdor, C.G.

    2018-01-01

    Cancer immunotherapy can successfully promote long-term anticancer immune responses, although there is still only a limited number of patients who benefit from such treatment, and it can sometimes have severe treatment-associated adverse events. Compared with systemic immunomodulation, local

  4. Effect of two doses of carbamylated allergoid extract of dust mite on nasal reactivity.

    Science.gov (United States)

    Scalone, G; Compalati, E; Bruno, M E; Mistrello, G

    2013-11-01

    Background and Objective. Single SLIT studies with native allergen extracts support a dose-response effect for clinical and immunological outcomes. Conversely for carbamylated allergoids this dose-response effects is less evident, likely because the threshold for efficacy is more easily reached through the enhanced bioavailability of the extract consequent to the selective chemical modification. Thus this pilot study investigates the dose-response effect on nasal specific reactivity and safety of two unusual doses of carbamylated allergoid in patients mono-sensitized to house dust mites. Methods. A prospective open randomized study involved 6-65 year-old Italian patients with clinically relevant sensitization to house dust mites and positive response to nasal provocation challenge. Monomeric carbamylated allergoid was delivered once daily at the dose of 1000 AU or 2000 AU from June to September 2009, during the lowest level of mites exposure. Primary outcomes were the change of the threshold of allergen concentration for a positive nasal provocation test (NPT) before and after the treatment and the product safety. Secondary outcome was the change  in the mean percentage fall of peak nasal inspiratory flow (PNIF) following nasal challenge. Results. Thirty-four patients were enrolled. Fifteen in group 1 and 14 in group 2 concluded the study. After 12 weeks all patients treated in group 1 and all but one in group 2 showed an increase in the threshold dose provoking a positive NPT. Those with no symptoms onset with the highest dose delivered were 80% in group 1 and 78.6% in group 2 (p=0.92). From first to second challenge, the mean percentage fall of PNIF  was reduced with no statistical difference between groups (p=0.95), and with no difference between the final mean percentage falls (p=0.65). No serious adverse reactions occurred and the frequency of events, all mild, was similar in the two groups. Conclusions. Twelve weeks of carbamylated sublingual allergoid

  5. Can Immunotherapy Succeed in Glioblastoma?

    Science.gov (United States)

    Researchers are hopeful that, for the deadly brain cancer glioblastoma, immunotherapy might succeed where other therapies have not. As this Cancer Currents post reports, different immunotherapy approaches are being tested in clinical trials.

  6. Immunotherapy of childhood Sarcomas

    Directory of Open Access Journals (Sweden)

    Stephen S Roberts

    2015-08-01

    Full Text Available Pediatric sarcomas are a heterogeneous group of malignant tumors of bone and soft tissue origin. Although more than 100 different histologic subtypes have been described, the majority of pediatric cases belong to the Ewing’s family of tumors, rhabdomyosarcoma and osteosarcoma. Most patients that present with localized stage are curable with surgery and/or chemotherapy; however, those with metastatic disease at diagnosis or those who experience a relapse continue to have a very poor prognosis. New therapies for these patients are urgently needed. Immunotherapy is an established treatment modality for both liquid and solid tumors, and in pediatrics, most notably for neuroblastoma and osteosarcoma. In the past, immunomodulatory agents such as interferon, interleukin-2, and Liposomal-muramyl  tripeptide phosphatidyl-ethanolamine (L-MTP have been tried, with some activity seen in subsets of patients; additionally, various cancer vaccines have been studied with possible benefit. Monoclonal antibody therapies against tumor antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA4 and PD-1 are being actively explored in pediatric sarcomas. Building on the success of adoptive T cell therapy for EBV-related lymphoma, strategies to redirect T cells using chimeric antigen receptors and bispecific antibodies are rapidly evolving with potential for the treatment of sarcomas. This review will focus on recent preclinical and clinical developments in targeted agents for pediatric sarcomas with emphasis on the immunobiology of immune checkpoints, immunoediting, tumor microenvironment, antibody engineering, cell engineering, and tumor vaccines. The future integration of antibody based and cell based therapies into an overall treatment strategy of sarcoma will be discussed.

  7. Immunotherapy for Gastroesophageal Cancer

    Directory of Open Access Journals (Sweden)

    Emily F. Goode

    2016-09-01

    Full Text Available Survival for patients with advanced oesophageal and stomach cancer is poor; together these cancers are responsible for more than a million deaths per year globally. As chemotherapy and targeted therapies such as trastuzumab and ramucirumab result in modest improvements in survival but not long-term cure for such patients, development of alternative treatment approaches is warranted. Novel immunotherapy drugs such as checkpoint inhibitors have been paradigm changing in melanoma, non-small cell lung cancer and urothelial cancers. In this review, we assess the early evidence for efficacy of immunotherapy in patients with gastroesophageal cancer in addition to considering biomarkers associated with response to these treatments. Early results of Anti- Programmed Cell Death Protein-1 (anti-PD-1, anti-PD-L1 and anti-Cytotoxic T-lymphocyte assosciated protein-4 (anti-CTLA4 trials are examined, and we conclude with a discussion on the future direction for immunotherapy for gastroesophageal cancer patients.

  8. The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment.

    Science.gov (United States)

    Rodríguez Del Río, Pablo; Vidal, Carmen; Just, Jocelyne; Tabar, Ana I; Sanchez-Machin, Inmaculada; Eberle, Peter; Borja, Jesus; Bubel, Petra; Pfaar, Oliver; Demoly, Pascal; Calderón, Moises A

    2017-02-01

    Safety data on 'real-life' allergen immunotherapy (AIT) in children and adolescents is usually extrapolated from studies in adults. Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospective European survey. Patient profiles and systemic reactions (SRs) were recorded. Descriptive, univariate and multivariate analyses were used to identify risk factors for SRs. A total of 1563 patients (mean ± SD age: 11.7 ± 3.9 years; rhinitis: 93.7%; asthma: 61.5%; polysensitization: 62.5%) and 1578 courses of AIT were assessed. Single-allergen AIT was administered in 89.5% of cases (n = 1412; mites: 49%; grass pollen: 25.8%; tree pollen: 8.7%; Alternaria: 4.6%; dander: 0.8%; weed pollen: 0.6%). Subcutaneous AIT (SCIT) was used in 71.4% (n = 1127) of the treatments, including 574 (50.9%) with natural extracts. Sublingual AIT (SLIT) was used for the remaining 451 treatments (drops: 73.8%; tablets: 26.2%). The mean ± SD follow-up period was 12.9 ± 3.3 months. The estimated total number of doses was 19,669 for SCIT and 131,550 for SLIT. Twenty-four patients (1.53%) experienced 29 SRs. Respiratory (55.7%) and skin symptoms (37.9%) were most frequent. Anaphylaxis was diagnosed in 3 SRs (10.3%), and adrenaline was administered in 2 of these cases. In a univariate analysis, the risk of SRs was lower in mite-sensitized patients and higher in cases of pollen polysensitization (>3), grass pollen extracts and the use of natural extracts (vs. allergoids). In a real-life paediatric setting, AIT is safe. SRs are infrequent and generally not severe. Pollen polysensitization, grass pollen extracts and natural extracts (vs. allergoids) were risk factors for AIT-associated SRs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. [Practice patterns in Mexican allergologists about specific immunotherapy with allergens].

    Science.gov (United States)

    Larenas Linnemann, Désirée; Guidos Fogelbach, Guillermo Arturo; Arias Cruz, Alfredo

    2008-01-01

    Immunotherapy has been practiced since over a hundred years. Since the first applications up today changes have occurred in the preparation, dose and duration of the treatment, as well as in the extracts used. Guidelines have been published in Mexico and other countries to try to unify these practice patterns of immunotherapy. By means of a questionnaire, sent in various occasions to all members of the Colegio Mexicano de Inmunología Clínica y Alergia (CMICA) and of the Colegio Mexicano de Pediatras, Especialistas en Inmunología y Alergia (CoMPedIA) we tried to get a picture of the daily practice patterns of immunotherapy in the allergist's office. Results will be presented in a descriptive manner. A response rate of 61 (17%) was obtained from the College members. For immunotherapy allergists use locally made and imported extracts, generally mixed in their office (20% over 10 allergens in one bottle). Eighty percent adds bacterial vaccine at some point and 60% uses sublingual immunotherapy. Most use Evans without albumin as diluent, don't routinely premedicate, reach maintenance treatment after more than six months and 46% recommends a maximum duration of immunotherapy of two years or less. We present a diagnosis on the current situation of practice patterns concerning allergen immunotherapy among the members of both Mexican colleges of allergists. The methods used by the allergists for indication, preparation and administration are quite diverse.

  10. Safety of allergen immunotherapy: a review of premedication and dose adjustment.

    Science.gov (United States)

    Morris, A Erika; Marshall, Gailen D

    2012-03-01

    From the first allergen immunotherapy proposed in the early 1900s to the present day, numerous studies have proven the efficacy of allergen immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity. The major risk, however small, with allergen immunotherapy is anaphylaxis. There has been considerable interest and debate regarding risk factors for immunotherapy reactions (local and systemic) and interventions to reduce the occurrence of these reactions. One of these interventions that is especially debated regards dose adjustment for various reasons, but in particular for local reactions. In this review, we discuss the safety of immunotherapy and provide a comprehensive review of the literature regarding immunotherapy schedules and doses.

  11. Sublingual allergen immunotherapy

    DEFF Research Database (Denmark)

    Calderón, M A; Simons, F E R; Malling, Hans-Jørgen

    2012-01-01

    To cite this article: Calderón MA, Simons FER, Malling H-J, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy 2012; 67: 302-311. ABSTRACT: Allergen immunotherapy reorients inappropriate immune responses......-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast...... cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical...

  12. Immunotherapy for tularemia

    Science.gov (United States)

    Skyberg, Jerod A.

    2013-01-01

    Francisella tularensis is a gram-negative bacterium that causes the zoonotic disease tularemia. Francisella is highly infectious via the respiratory route (~10 CFUs) and pulmonary infections due to type A strains of F. tularensis are highly lethal in untreated patients (>30%). In addition, no vaccines are licensed to prevent tularemia in humans. Due to the high infectivity and mortality of pulmonary tularemia, F. tularensis has been weaponized, including via the introduction of antibiotic resistance, by several countries. Because of the lack of efficacious vaccines, and concerns about F. tularensis acquiring resistance to antibiotics via natural or illicit means, augmentation of host immunity, and humoral immunotherapy have been investigated as countermeasures against tularemia. This manuscript will review advances made and challenges in the field of immunotherapy against tularemia. PMID:23959031

  13. Immunotherapy With Magentorheologic Fluids

    Science.gov (United States)

    2011-08-01

    anti-tumor effects are weakened by removal of the tumor antigen pool (i.e. surgery) or use of cytoreductive and immunosuppressive therapies (i.e...particles were injected as magneto -rheological fluid (MRF) into an orthotopic primary breast cancer and followed by application of a magnetic field to...SUBJECT TERMS MRF: Magneto -rehological fluid iron particles, IT: immunotherapy, necrotic death, DCs: dendritic cells, cytokines, chemokines

  14. Immunotherapy in genitourinary malignancies

    Directory of Open Access Journals (Sweden)

    Kathan Mehta

    2017-04-01

    Full Text Available Abstract Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body’s own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.

  15. Allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Moote William

    2011-11-01

    Full Text Available Abstract Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. However, despite its proven efficacy in these conditions, it is frequently underutilized in Canada. The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, the adverse effects of pharmacological treatment, and patient preferences. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, injections must be given under medical supervision in clinics that are equipped to manage anaphylaxis. In this article, the authors review the indications and contraindications, patient selection criteria, and the administration, safety and efficacy of allergen-specific immunotherapy.

  16. EAACI Guidelines on allergen immunotherapy

    DEFF Research Database (Denmark)

    Pajno, G B; Fernandez-Rivas, M; Arasi, S

    2018-01-01

    . This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery...

  17. Orphan immunotherapies for allergic diseases.

    Science.gov (United States)

    Ridolo, Erminia; Montagni, Marcello; Incorvaia, Cristoforo; Senna, Gianenrico; Passalacqua, Giovanni

    2016-03-01

    As confirmed by systematic reviews and meta-analyses, allergen immunotherapy is clinically effective in the treatment of allergic diseases. In particular, subcutaneous immunotherapy is a pivotal treatment in patients with severe reactions to Hymenoptera venom, whereas subcutaneous immunotherapy and sublingual immunotherapy are indicated in the treatment of allergic rhinitis and asthma by inhalant allergens. Other allergies related to animal dander (other than cat, which is the most studied), such as dog, molds, occupational allergens, and insects, have also been recognized. For these allergens, immunotherapy is poorly studied and often unavailable. Thus, use of the term orphan immunotherapies is appropriate. We used MEDLINE to search the medical literature for English-language articles. Randomized, controlled, masked studies for orphan immunotherapies were selected. In the remaining cases, the available reports were described. The literature on food desensitization is abundant, but for other orphan allergens, such as mosquito, Argas reflexus, dog, or occupational allergens, there are only a few studies, and most are small studies or case reports. Orphan immunotherapy is associated with insufficient evidence of efficacy from controlled trials, an erroneous belief of the limited importance of some allergen sources, and the unlikelihood for producers to have a profit in making commercially available extracts (with an expensive process for registration) to be used in few patients. It should be taken into consideration that adequate preparations should be available also for orphan allergens. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Progress in research on combination treatment of cancer with radiation therapy and immunotherapy

    International Nuclear Information System (INIS)

    Wang Hao; Jia Rui; Yan Jinqi; Yu Jiyun

    2007-01-01

    Radiation therapy (RT) is an important local treatment for tumors, and immunotherapy is a systematic treatment. Combination of RT with immunotherapy may bring about an obvious synergistic anti-tumor effort. Here the research progress in this aspect is reviewed. (authors)

  19. Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma.

    Science.gov (United States)

    Kamat, Ashish M; Bellmunt, Joaquim; Galsky, Matthew D; Konety, Badrinath R; Lamm, Donald L; Langham, David; Lee, Cheryl T; Milowsky, Matthew I; O'Donnell, Michael A; O'Donnell, Peter H; Petrylak, Daniel P; Sharma, Padmanee; Skinner, Eila C; Sonpavde, Guru; Taylor, John A; Abraham, Prasanth; Rosenberg, Jonathan E

    2017-08-15

    The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression. However, these reports have not penetrated the community, and many patients do not receive appropriate therapy. Additionally, several immune checkpoint inhibitors have recently been approved for treatment of metastatic disease. The approval of immune checkpoint blockade for patients with platinum-resistant or -ineligible metastatic bladder cancer has led to considerations of expanded use for both advanced and, potentially, localized disease. To address these issues and others surrounding the appropriate use of immunotherapy for the treatment of bladder cancer, the Society for Immunotherapy of Cancer (SITC) convened a Task Force of experts, including physicians, patient advocates, and nurses, to address issues related to patient selection, toxicity management, clinical endpoints, as well as the combination and sequencing of therapies. Following the standard approach established by the Society for other cancers, a systematic literature review and analysis of data, combined with consensus voting was used to generate guidelines. Here, we provide a consensus statement for the use of immunotherapy in patients with bladder cancer, with plans to update these recommendations as the field progresses.

  20. CCL21 Cancer Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yuan, E-mail: yuanlin@mednet.ucla.edu [Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); UCLA Head and Neck Cancer Program, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Sharma, Sherven [Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Veterans’ Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073 (United States); John, Maie St. [Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); UCLA Head and Neck Cancer Program, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)

    2014-05-07

    Cancer, a major health problem, affects 12 million people worldwide every year. With surgery and chemo-radiation the long term survival rate for the majority of cancer patients is dismal. Thus novel treatments are urgently needed. Immunotherapy, the harnessing of the immune system to destroy cancer cells is an attractive option with potential for long term anti-tumor benefit. Cytokines are biological response modifiers that stimulate anti-tumor immune responses. In this review, we discuss the anti-tumor efficacy of the chemotactic cytokine CCL21 and its pre-clinical and clinical application in cancer.

  1. Immunotherapy of Cryptococcus infections.

    Science.gov (United States)

    Antachopoulos, C; Walsh, T J

    2012-02-01

    Despite appropriate antifungal treatment, the management of cryptococcal disease remains challenging, especially in immunocompromised patients, such as human immunodeficiency virus-infected individuals and solid organ transplant recipients. During the past two decades, our knowledge of host immune responses against Cryptococcus spp. has been greatly advanced, and the role of immunomodulation in augmenting the response to infection has been investigated. In particular, the role of 'protective' Th1 (tumour necrosis factor-α, interferon (IFN)-γ, interleukin (IL)-12, and IL-18) and Th17 (IL-23 and IL-17) and 'non-protective' Th2 (IL-4, IL-10, and IL-13) cytokines has been extensively studied in vitro and in animal models of cryptococcal infection. Immunomodulation with monoclonal antibodies against the capsular polysaccharide glucuronoxylomannan, glucosylceramides, melanin and β-glucan and, lately, with radioimmunotherapy has also yielded promising results in animal models. As a balance between sufficiently protective Th1 responses and excessive inflammation is important for optimal outcome, the effect of immunotherapy may range from beneficial to deleterious, depending on factors related to the host, the infecting organism, and the immunomodulatory regimen. Clinical evidence supporting immunomodulation in patients with cryptococcal infection remains too limited to allow firm recommendations. Limited human data suggest a role for IFN-γ. Identification of surrogate markers characterizing patients' immunological status could possibly suggest candidate patients for immunotherapy and the type of immunomodulation to be administered. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  2. Conference Scene: novelties in immunotherapy.

    Science.gov (United States)

    Mitsias, Dimitris I; Kalogiros, Lampros A; Papadopoulos, Nikolaos G

    2013-10-01

    The only method aiming to permanently cure allergic disorders is allergen immunotherapy. Over the last 20 years there has been great progress in understanding the mechanisms that govern allergen immunotherapy in order to meet three basic prerequisites: safety, effectiveness and compliance. In the present summary report from the European Academy of Allergology and Clinical Immunology-World Allergy Organization Congress held last June in Milan, we review key points concerning the main axes as diagnosis, novel modalities, routes and protocols, as well as two important immunotherapy fields: food and insect venom allergy.

  3. EAACI Guidelines on Allergen Immunotherapy

    DEFF Research Database (Denmark)

    Sturm, Gunter J; Varga, Eva-Maria; Roberts, Graham

    2018-01-01

    and adults to prevent further moderate to severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline auto-injector. This guideline aims to give...... practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence. This article...

  4. Immunotherapies in CLL.

    Science.gov (United States)

    Park, Jae H; Brentjens, Renier J

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed leukemia in the Western world, yet remains essentially incurable. Although initial chemotherapy response rates are high, patients invariably relapse and subsequently develop resistance to chemotherapy. For the moment, allogeneic hematopoietic stem cell transplant (allo-HSCT) remains the only potentially curative treatment for patients with CLL, but it is associated with high rates of treatment-related mortality. Immune-based treatment strategies to augment the cytotoxic potential of T cells offer exciting new treatment options for patients with CLL, and provide a unique and powerful spectrum of tools distinct from traditional chemotherapy. Among the most novel and promising of these approaches are chimeric antigen receptor (CAR)-based cell therapies that combine advances in genetic engineering and adoptive immunotherapy.

  5. Gut Bacteria Affect Immunotherapy Response

    Science.gov (United States)

    Three new studies have identified intestinal bacteria that appear to influence the response to checkpoint inhibitors. This Cancer Currents blog post explains how the researchers think their findings could be used to improve patients’ responses to these immunotherapy drugs.

  6. 3D Models of Immunotherapy

    Science.gov (United States)

    This collaborative grant is developing 3D models of both mouse and human biology to investigate aspects of therapeutic vaccination in order to answer key questions relevant to human cancer immunotherapy.

  7. NCI's Role in Immunotherapy Research

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... promising immunotherapies to the clinic more efficiently and cost effectively. For ... of the checkpoint inhibitor pembrolizumab in patients with ...

  8. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  9. Immunotherapy and Immune Evasion in Prostate Cancer

    International Nuclear Information System (INIS)

    Thakur, Archana; Vaishampayan, Ulka; Lum, Lawrence G.

    2013-01-01

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies

  10. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

    2013-05-24

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

  11. Cellular immunotherapy for soft tissue sarcomas

    Science.gov (United States)

    Finkelstein, Steven Eric; Fishman, Mayer; Conley, Anthony P.; Gabrilovich, Dmitry; Antonia, Scott; Chiappori, Alberto

    2015-01-01

    SUMMARY Soft tissue sarcomas are rare neoplasms, with approximately 9,000 new cases in the United States every year. Unfortunately, there is little progress in the treatment of metastatic soft tissue sarcomas in the past two decades beyond the standard approaches of surgery, chemotherapy, and radiation. Immunotherapy is a modality complementary to conventional therapy,. It is appealing because functional anti-tumor activity could affect both local-regional and systemic disease and act over a prolonged period of time. In this report, we review immunotherapeutic investigative strategies being developed, including several tumor vaccine, antigen vaccine, and dendritic cell vaccine strategies. PMID:22401634

  12. Immunotherapy of allergic contact dermatitis.

    Science.gov (United States)

    Spiewak, Radoslaw

    2011-08-01

    The term 'immunotherapy' refers to treating diseases by inducing, enhancing or suppressing immune responses. As allergy is an excessive, detrimental immune reaction to otherwise harmless environmental substances, immunotherapy of allergic disease is aimed at the induction of tolerance toward sensitizing antigens. This article focuses on the historical developments, present state and future outlook for immunotherapy with haptens as a therapeutic modality for allergic contact dermatitis. Inspired by the effectiveness of immunotherapy in respiratory allergies, attempts were undertaken at curing allergic contact dermatitis by means of controlled administration of the sensitizing haptens. Animal and human experiments confirmed that tolerance to haptens can be induced most effectively when the induction of tolerance precedes attempted sensitization. In real life, however, therapy is sought by people who are already sensitized and an effective reversal of hypersensitivity seems more difficult to achieve. Decades of research on Rhus hypersensitivity led to a conclusion that immunotherapy can suppress Rhus dermatitis, however, only to a limited degree, for a short period of time, and at a high risk of side effects, which makes this method therapeutically unprofitable. Methodological problems with most available studies of immunotherapy of contact allergy to nickel make any definite conclusions impossible at this stage.

  13. Experimental study on active specific immunotherapy modified with irradiation

    International Nuclear Information System (INIS)

    Imanaka, Kazufumi; Ogawa, Yasuhiro; Gose, Kyuhei; Imajo, Yoshinari; Kumura, Shuji

    1982-01-01

    We have already reported that the effectiveness of active specific immunotherapy using irradiated tumor cells and infiltrating mononuclear cells which were separated from the topical tumor tissue 7 days after irradiation of 2,000 rad in experimental study. The present study was designed to investigate the effect of non-specific immunopotentiator PS-K combined with active specific immunotherapy. Female C3H/He mice aged 12 weeks were inoculated 4 x 10 6 MM 46 tumor cells in the right hind paws and received local electron irradiation with the dose of 3,000 rad on the 5th day after irradiation. Active specific immunotherapy was performed on the 12th day, and daily dose of 200 mg/kg of PS-K was injected intraperitoneally from the 6th day to the 10th day. The inhibition of the tumor growth and the elongation of survival period were noted in the group which received active specific immunotherapy combined with non-specific immunopotentiator, PS-K compared with the active specific immunotherapy alone. (author)

  14. IgG binding of mugwort pollen allergens and allergoids exposed to simulated gastrointestinal conditions measured by a self-developed ELISA test

    Directory of Open Access Journals (Sweden)

    RATKO M. JANKOV

    2004-07-01

    Full Text Available This study considers the influence of exposure to simulated gastrointestinal conditions (saliva, gut, intestine and acidic conditions of the gut on IgG binding of unmodified allergens and three types of LMW allergoids of Artemisia vulgaris pollen extract obtained by means of potassium cyanate, succinic and maleic anhydride. It also concerns the optimization of a self-developed ELISA assay for comparison of the specific IgG binding of mugwort pollen extract and modified mugwort pollen derivatives. The ELISA was conducted with a mugwort pollen extract coupled to the plate, using the sera from 12 mugwort-pollen allergic patients. The exposure to saliva fluid for 2 min did not influence the IgG binding properties of allergens and allergoids. Exposure of mugwort pollen allergens and LMW allergoids to the acidic conditions of the gut did not dramatically change their IgG binding properties. By exposing mugwort pollen extract and LMW derivatives to the SGF conditions for 1 h, the percent of IgG binding epitopes was reduced to a half of its starting value in the extract and to about 30 % in all the allergoid samples. After prolonged exposure only the carbamyl derivative showed reduced IgG binding. Changes of the IgG binding potential of all four samples after exposure in SIF followed a similar pattern.

  15. Development of cancer immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y

    1999-04-01

    To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy.

  16. Development of cancer immunotherapy

    International Nuclear Information System (INIS)

    Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y.

    1999-04-01

    To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy

  17. Allergen immunotherapy for allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Nurmatov, Ulugbek; Dhami, Sangeeta; Arasi, Stefania

    2017-01-01

    Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effective......Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence...... of these were judged to be of high, five moderate and three low quality. These reviews suggested that, in carefully selected patients, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy resulted in significant reductions in symptom scores and medication requirements. Serious adverse outcomes were rare...

  18. Salvage immunotherapy of malignant glioma.

    Science.gov (United States)

    Ingram, M; Jacques, S; Freshwater, D B; Techy, G B; Shelden, C H; Helsper, J T

    1987-12-01

    We present the preliminary results of a phase I trial of adoptive immunotherapy for recurrent or residual malignant glioma. The protocol is based on surgical debulking followed by implantation into the tumor bed of autologous lymphocytes that have been stimulated with phytohemagglutinin-P and then cultured in vitro in the presence of interleukin 2. Fifty-five patients with a mean Karnofsky rating of 64 were treated between February 1985 and March 1987. No significant toxicity was associated with the immunotherapy. Fifty patients had a positive initial response to therapy, nine patients had early recurrence (two to four months after treatment), and 22 patients died. We comment on major differences between the protocol described and other immunotherapy protocols.

  19. Immunotherapy of distant metastatic disease

    DEFF Research Database (Denmark)

    Schadendorf, D; Algarra, S M; Bastholt, L

    2009-01-01

    Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated with signif......Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated...

  20. Hypoallergenic molecules for subcutaneous immunotherapy

    DEFF Research Database (Denmark)

    Jongejan, Laurian; van Ree, Ronald; Poulsen, Lars K

    2016-01-01

    Although a large part of the population suffers from allergies, a cure is not yet available. Allergen-specific immunotherapy (AIT) offers promise for these patients. AIT has proven successful in insect and venom allergies; however, for food allergy this is still unclear. In this editorial we focus...... on the recent advances in a proof of concept study in food allergy, FAST (Food allergy specific immunotherapy), which may increase interest within the biomolecular and pharmaceutical industry to embark on similar projects of immunology driven precision medicine within the allergy field....

  1. Hypoallergenic molecules for subcutaneous immunotherapy.

    Science.gov (United States)

    Jongejan, Laurian; van Ree, Ronald; Poulsen, Lars K

    2016-01-01

    Although a large part of the population suffers from allergies, a cure is not yet available. Allergen-specific immunotherapy (AIT) offers promise for these patients. AIT has proven successful in insect and venom allergies; however, for food allergy this is still unclear. In this editorial we focus on the recent advances in a proof of concept study in food allergy, FAST (Food allergy specific immunotherapy), which may increase interest within the biomolecular and pharmaceutical industry to embark on similar projects of immunology driven precision medicine within the allergy field.

  2. Allergen immunotherapy for allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Dhami, Sangeeta; Nurmatov, Ulugbek; Roberts, Graham

    2016-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT...

  3. Hypoallergenic molecules for subcutaneous immunotherapy

    NARCIS (Netherlands)

    Jongejan, Laurian; van Ree, Ronald; Poulsen, Lars K.

    2016-01-01

    Although a large part of the population suffers from allergies, a cure is not yet available. Allergen-specific immunotherapy (AIT) offers promise for these patients. AIT has proven successful in insect and venom allergies; however, for food allergy this is still unclear. In this editorial we focus

  4. ALLERGEN-SPECIFIC IMMUNOTHERAPY: VACCINES FOR ALLERGIC DISEASES

    Directory of Open Access Journals (Sweden)

    A. S. Fedorov

    2015-01-01

    via increased production of specific IgG antibodies, primarily of IgG4 subtype. The shift of balance between IgE and IgG4 towards IgG4 production is now considered a fundamental condition for successful ASIT. It has been proven that the allergen-specific IgG4 antibodies against IgE persist after discontinuation of the treatment and can provide long-term clinical tolerance. Modern prospectives for development of new forms and species of preparations for ASIT are also reviewed. Two groups of drugs for ASIT have been adopted for clinical practice until now, i.e., allergens and allergoids (allergens chemically modified by treatment with formaldehyde, in order to enhance their immunogenicity and to reduce the incidence of adverse allergic reactions associated with their application. Immunological mechanisms of SLIT (sublingual immunotherapy are subjected to special consideration. So far, SLIT is the safest and most promising option of ASIT today, its usage is most expedient in pediatric practice.

  5. Experimental study of an active specific immunotherapy modified with irradiation, 2

    International Nuclear Information System (INIS)

    Imanaka, Kazufumi; Ogawa, Yasuhiro; Takashima, Hitoshi

    1982-01-01

    We had demonstrated in the former investigation that the strongest local infiltration of T-lymphocytes was observed in C3H/He mice transplanted MM46 at seven days after irradiation with the dose of 2,000 rads. This result indicated that the enhancement of the antigenicity of tumor cells was attained after low-dose-irradiation. We had also reported that specific active immunotherapy using low-dose-irradiated tumor cells and activated mononuclear cells after radiotherapy was effective on the elongation of survival period. In this paper, we studied whether the tumor cell inoculated after active specific immunotherapy was inhibited or not. Active specific immunotherapy using tumor cells and mononuclear cells was performed on female C3H/He mice aged 12 weeks in the left hind paws. Tumor cells and mononuclear cells were separated from the tumor tissue on the 12th day since inoculation of 5 x 10 6 of MM46 tumor cells which were irradiated with the dose of 2,000 rads of 3,000 rads by high energy electron beam on the fifth day. Seven days after active specific immunotherapy 1 x 10 5 or 1 x 10 6 of tumor cell were i noculated in the right hind paws of mice which received active specific immunotherapy. Anti-tumor effect was evaluated by the changes of tumor volume and survival rate. The tumor volume of the group which received active specific immunotherapy was smaller than that without active specific immunotherapy for about nine days since inoculation. Fifty-day survival rate was significantly higher in the group which received active specific immunotherapy compared with the group without immunotherapy (p < 0.01). (author)

  6. Radio-immunotherapy of solid tumors

    International Nuclear Information System (INIS)

    Chatal, J.F.; Faivre Chauvet, A.; Bardies, M.; Kraeber-Bodere, F.; Barbet, J.

    2001-01-01

    A convincing efficacy of radio-immunotherapy of solid tumors has not been documented yet in clinical studies. Consequently, a methodological optimization is needed within the scope in increasing absorbed doses delivered to tumor targets by amplifying cumulative tumor activity and in the same time in reducing absorbed doses delivered normal organs. Multi-step pre-targeting techniques allow to approach these goals. The most developed technique is based on the high affinity for biotin. In a first step an anti-tumor antibody coupled to avidin or biodin is injected. In a second step, 24 hours later, the circulating residual immuno-conjugate is bound to a molecular complex and eliminated through the reticulo endothelial system of the liver ('chase'phase). A third step, a few hours later, consists in injecting biotin coupled to DOTA chelating agent and labeled with yttrium 90. This small molecule rapidly diffuses to tumor targets and binds to pre-localized immuno-conjugate. Another technique, designed and developed in France, is based on antigen-antibody affinity. In a first step an anti-tumor / anti-hapten bi-specific antibody is injected and, in a second step, a few days later, the small hapten molecule is radiolabeled with I-131 and injected. It diffuses rapidly to the tumor targets and binds to the anti-hapten arm of the pre-localized bi-specific antibody. An alternative way to increase radio-immunotherapy efficacy consists in combining this low-dose rate irradiation to radiosensitizing molecules within the scope of an additive or supra additive effect which has previously documented. (author)

  7. IgG binding of mugwort pollen allergens and allergoids exposed to simulated gastrointestinal conditions measured by a self-developed ELISA test

    OpenAIRE

    RATKO M. JANKOV; OLGA VUCKOVIC; DANICA DJERGOVIC-PETROVIC; LIDIJA BURAZER; TANJA D. CIRKOVICVELICKOVIC; MARIJA DJ. GAVROVIC-JANKULOVIC; NATALIJA DJ. POLOVIC

    2004-01-01

    This study considers the influence of exposure to simulated gastrointestinal conditions (saliva, gut, intestine and acidic conditions of the gut) on IgG binding of unmodified allergens and three types of LMW allergoids of Artemisia vulgaris pollen extract obtained by means of potassium cyanate, succinic and maleic anhydride. It also concerns the optimization of a self-developed ELISA assay for comparison of the specific IgG binding of mugwort pollen extract and modified mugwort pollen derivat...

  8. Allergy immunotherapy with a hypoallergenic recombinant birch pollen allergen rBet v 1-FV in a randomized controlled trial.

    Science.gov (United States)

    Klimek, Ludger; Bachert, Claus; Lukat, Karl-Friedrich; Pfaar, Oliver; Meyer, Hanns; Narkus, Annemie

    2015-01-01

    Pollen extracts and chemically modified allergoids are used successfully in allergen immunotherapy (AIT). Recombinant extracts offer potential advantages with respect to pharmaceutical quality, standardization and dosing. A hypoallergenic recombinant folding variant of the major birch pollen allergen (rBet v 1-FV) was compared with an established native birch preparation. A pre-seasonal, randomized, actively controlled phase II study was performed in birch pollen allergic rhino-conjunctivitis with or without asthma, GINA I/ II. 51 patients (24 rBet v 1-FV, 27 native extract) started therapy with subcutaneous allergen immunotherapy (SCIT). Primary end-point was a combined symptom medication score (SMS), changes in nasal provocation test, visual rating score and specific antibody responses secondary end-points. After one pre-seasonal treatment course the combined SMS was 5.86 (median; IQR: 14.02) for the rBet v 1-FV group versus 12.40 (median; IQR: 9.32) for the comparator during the three weeks pollen season (p = 0.330). After treatment in the second year, scores were 3.00 (median; IQR: 6.50) and 2.93 (4.86) respectively. Allergen tolerance in a nasal provocation test improved to a comparable extent in both groups. Significant increases in birch pollen-specific IgG1 and IgG4 were observed in both treatment groups following the first treatment phase and remained significantly raised until the end of the study. In this first in man, proof of concept phase II trial no statistical difference between rBet v 1-FV and an established natural pollen extract could be observed. rBet v 1-FV could be administered in higher doses than the native protein with no increase in adverse effects. The study was registered in clinicalTrials.gov (NCT00266526).

  9. Lentiviral vectors in cancer immunotherapy.

    Science.gov (United States)

    Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

    2015-01-01

    Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.

  10. Specific immunotherapy ameliorates ulcerative colitis.

    Science.gov (United States)

    Cai, Min; Zeng, Lu; Li, Lin-Jing; Mo, Li-Hua; Xie, Rui-Di; Feng, Bai-Sui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

    2016-01-01

    Hypersensitivity reaction to certain allergens plays a role in the pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the effect of specific immunotherapy in a group of IBD patients. Patients with both ulcerative colitis (UC) and food allergy were recruited into this study. Food allergy was diagnosed by skin prick test and serum specific IgE. The patients were treated with specific immunotherapy (SIT) and Clostridium butyricum (CB) capsules. After treating with SIT and CB, the clinical symptoms of UC were markedly suppressed as shown by reduced truncated Mayo scores and medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor necrosis factor (TNF)-α were also suppressed. Treating with SIT alone or CB alone did not show appreciable improvement of the clinical symptoms of UC. UC with food allergy can be ameliorated by administration with SIT and butyrate-production probiotics.

  11. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie

    2012-01-01

    Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC...... and presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along...

  12. EAACI Guidelines on Allergen Immunotherapy

    DEFF Research Database (Denmark)

    Halken, Susanne; Larenas-Linnemann, Desiree; Roberts, Graham

    2017-01-01

    Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) ...... of allergic co-morbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease modifying treatment exists but there is an urgent need for more high-quality clinical trials....

  13. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2016-09-01

    TITLE AND SUBTITLE 5a. CONTRACT NUMBER Integrated Immunotherapy for Breast Cancer 5b. GRANT NUMBER W81XWH-12-1-0366 5c. PROGRAM ELEMENT...communications 215, 566 (Oct 13, 1995). 87. S. J. Reshkin, R. A. Cardone , S. Harguindey, Na+-H+ exchanger, pH regulation and cancer. Recent patents on anti-cancer drug discovery 8, 85 (Jan 1, 2013).

  14. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 7

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji; Yamamoto, Yoichi; Morita, Masaru

    1983-01-01

    We have already reported the remarkable effect of the active specific immunotherapy utilizing cryopreserved tumor cells and infiltrating mononuclear cells prepared from a lowdose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, PSK combined with this active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor cells were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the fifth day after tumor inoculation. This active specific immunotherapy was performed on the twelveth day, and daily dose of 200 mg/kg of PSK was injected intraperitoneally from the sixth day to the tenth day. The more inhibition of the tumor growth was observed in the group which received this active specific immunotherapy combined with a biological response modifier, PSK compared with that received this active specific immunotherapy alone. (author)

  15. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 5

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Imanaka, Kazufumi; Gose, Kyuhei; Imajo, Yoshinari; Kimura, Shuji

    1982-01-01

    We have already reported the remarkable effect of the active specific immunotherapy utilizing cryopreserved tumor cells and infiltrating mononuclear cells prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, OK-432 combined with this active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor cells were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the sixth day after inoculation. This active specific immunotherapy was performed on the thirteenth day, and daily dose of 1.0 KE of OK-432 was injected intraperitoneally from the thirteenth day to the seventeenth day. The inhibition of the tumor growth was observed in the group which received this active specific immunotherapy combined with a biological response modifier, OK-432 compared with that received this active specific immunotherapy alone. (author)

  16. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 4

    International Nuclear Information System (INIS)

    Imanaka, Kazufumi; Ogawa, Yasuhiro; Gose, Kyuhei; Imajo, Yoshinari; Kimura, Shuji

    1982-01-01

    We have already reported that the effectiveness of active specific immunotherapy using low-dose irradiated tumor cells and infiltrating mononuclear cells. The present study was designed to investigate the effect of non-specific immunopotentiator combined with the active specific immunotherapy. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the sixth day after inoculation. Active specific immunotherapy was performed on the 13th day, and daily dose of 1.0 KE of OK-432 was injected intraperitoneally from the 13th day to the 17th day. The inhibition of the tumor growth and the elongation of survival period were noted in the group which received active specific immunotherapy combined with non-specific immunopotentiator, OK-432 compared with that active specific immunotherapy alone. (author)

  17. Immunotherapy Targets in Pediatric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal, E-mail: rimas.orentas@nih.gov, E-mail: mackallc@mail.nih.gov [Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)

    2012-01-30

    Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.

  18. Immunotherapy Targets in Pediatric Cancer

    International Nuclear Information System (INIS)

    Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

    2012-01-01

    Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.

  19. Parasites and immunotherapy: with or against?

    Science.gov (United States)

    Yousofi Darani, Hossein; Yousefi, Morteza; Safari, Marzieh; Jafari, Rasool

    2016-06-01

    Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewed.

  20. Advances and highlights in allergen immunotherapy: On the way to sustained clinical and immunologic tolerance.

    Science.gov (United States)

    Berings, Margot; Karaaslan, Cagatay; Altunbulakli, Can; Gevaert, Philippe; Akdis, Mübeccel; Bachert, Claus; Akdis, Cezmi A

    2017-11-01

    Allergen immunotherapy (AIT) is an effective treatment strategy for allergic diseases and has been used for more than 100 years. In recent years, however, the expectations on concepts, conduct, statistical evaluation, and reporting have developed significantly. Products have undergone dose-response and confirmative studies in adults and children to provide evidence for the optimal dosage, safety, and efficacy of AIT vaccines using subcutaneous and sublingual delivery pathways in large patient cohorts, ensuring solid conclusions to be drawn from them for the advantage of patients and societies alike. Those standards should be followed today, and products answering to them should be preferred over others lacking optimization and proof of efficacy and safety. Molecular and cellular mechanisms of AIT include early mast cell and basophil desensitization effects, regulation of T- and B-cell responses, regulation of IgE and IgG 4 production, and inhibition of responses from eosinophils, mast cells, and basophils in the affected tissues. There were many developments to improve vaccination strategies, demonstration of new molecules involved in molecular mechanisms, and demonstration of new biomarkers for AIT during the last few years. The combination of probiotics, vitamins, and biological agents with AIT is highlighting current advances. Development of allergoids and recombinant and hypoallergenic vaccines to skew the immune response from IgE to IgG 4 and regulation of dendritic cell, mast cell, basophil, innate lymphoid cell, T-cell, and B-cell responses to allergens are also discussed in detail. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Research advances in cellular immunotherapy for primary hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHANG Ye

    2014-09-01

    Full Text Available The present therapy for primary hepatocellular carcinoma (HCC consists of surgery as well as local radiotherapy and chemotherapy. However, the majority of patients are susceptible to recurrence after comprehensive treatment, and the overall treatment outcome is not ideal due to the lack of effective drugs and strategies. Increasing evidence has demonstrated that the immune system is closely related to the development, progression, metastasis, and recurrence of HCC. Thus, immune therapy, especially cellular immunotherapy, could regulate immune function and induce specific antitumor immunity to achieve the goal of controlling HCC and reducing its recurrence and metastasis, which has become an essential part in the comprehensive treatment of HCC. The findings in preclinical and clinical studies on cellular immunotherapy for HCC data are reviewed, and the current problems are discussed.

  2. Advances in immunotherapy for bladder cancer

    International Nuclear Information System (INIS)

    Zhao Jiyu; Chen Lijun

    2009-01-01

    The conventional treatments for bladder cancer, including surgery, chemotherapy and radiotherapy, are highly invasive and bring about lots of side effects. Immunotherapy has become a promising strategy for the treatment of malignant tumors. This review presents the research advances in immunotherapy of bladder cancer. (authors)

  3. Polymeric particulate systems for immunotherapy of cancer

    NARCIS (Netherlands)

    Rahimian, S.

    2015-01-01

    Immunotherapy has been established as a groundbreaking approach to treat cancer. It involves modulation of the host’s immune response to fight cancer. This is achieved by either enhancing tumor-specific T cell responses or inhibition of the tumor-induced immune suppression. Immunotherapy, however

  4. Recombinant pollen allergens from Dactylis glomerata: preliminary evidence that human IgE cross-reactivity between Dac g II and Lol p I/II is increased following grass pollen immunotherapy.

    Science.gov (United States)

    Roberts, A M; Van Ree, R; Cardy, S M; Bevan, L J; Walker, M R

    1992-07-01

    We previously described the isolation of three identical complementary DNA (cDNA) clones, constructed from Orchard/Cocksfoot grass (Dactylis glomerata) anther messenger RNA (mRNA), expressing a 140,000 MW beta-galactosidase fusion protein recognized by IgE antibodies in atopic sera. Partial nucleotide sequencing and inferred amino acid sequence showed greater than 90% homology with the group II allergen from Lolium perenne (Lol II) indicating they encode the group II equivalent, Dac g II. Western blot immunoprobing of recombinant lysates with rabbit polyclonal, mouse monoclonal and human polyclonal antisera demonstrates immunological identity between recombinant Dac g II, Lol p I and Lol p II. Similar cross-identity is observed with pollen extracts from three other grass species: Festuca rubra, Phleum pratense and Anthoxanthum odoratum. Recombinant Dac g II was recognized by species- and group-cross-reactive human IgE antibodies in 33% (4/12) of sera randomly selected from grass-sensitive individuals and in 67% (14/21) of sera from patients receiving grass pollen immunotherapy, whilst 0/4 sera from patients receiving venom immunotherapy alone contained Dac g II cross-reactive IgE. Cross-reactive IgG4 antibodies were detectable in 95% of sera from grass pollen immunotherapy patients. These preliminary data suggest that conventional grass pollen allergoid desensitization immunotherapy may induce IgE responses to a cross-reactive epitope(s) co-expressed by grass pollen groups I and II (and possibly group III) allergens.

  5. New Horizons in Allergen Immunotherapy

    DEFF Research Database (Denmark)

    Backer, Vibeke

    2016-01-01

    . The authors concluded that among adultswithHDMallergy–related asthma not well controlled by ICS, the addition of HDM SLIT deliveredas a once-daily tablet significantly prolongedthetime to the first asthma exacerbation during ICS reduction. Aswith any clinical trial, the critical question is howmeaningful...... the active therapycomparedwith placebowhendifferent criteriawere used todefine asthma exacerbations, aswell as in immunologic changes consistentwith desensitization.However, therewerenosignificantdifferences inpatients’ responses toquestionnairesregardingeitherasthmacontrolorqualityoflife. The authors...... treatmentwith ICS. The authors’ choice of a primary end point based on exacerbations during ICS reduction is also unique to immunotherapy trials,with previous trials ofHDMimmunotherapy focusing onmedication requirements, symptomsscores, or lung function as primary end points. Furthermore, the inclusion...

  6. Autoimmunity and Immunotherapy in Narcolepsy

    Directory of Open Access Journals (Sweden)

    Min Jae Seong

    2017-06-01

    Full Text Available Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. Narcolepsy is caused by damage of hypocretin producing neurons in the lateral hypothalamus. The association of narcolepsy with HLA DQB1*0602 and high incidence following H1N1 pandemic in china, vaccination with pandemrix and an adjuvanted H1N1 vaccine suggests that pathophysiology of narcolepsy is involved in the immune system. This review focused on immunological associations and immunotherapy in narcolepsy.

  7. Side effects during subcutaneous immunotherapy in children with allergic diseases.

    Science.gov (United States)

    Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

    2018-05-01

    Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  8. Cancer immunotherapy and immunological memory.

    Science.gov (United States)

    Murata, Kenji; Tsukahara, Tomohide; Torigoe, Toshihiko

    2016-01-01

    Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy.

  9. Mosquito bite anaphylaxis: immunotherapy with whole body extracts.

    Science.gov (United States)

    McCormack, D R; Salata, K F; Hershey, J N; Carpenter, G B; Engler, R J

    1995-01-01

    Adverse reactions to mosquito bites have been recognized for some time. These usually consist of large local swellings and redness, generalized urticaria, angioedema and less easily definable responses such as nausea, dizziness, headaches, and lethargy. We report two patients who experienced systemic anaphylaxis from mosquito bites. Both were skin tested and given immunotherapy using whole body mosquito extracts. Skin testing using whole body mosquito extracts was positive to Aedes aegypti at 1/1,000 weight/volume (wt/vol) in one patient and to Aedes aegypti at 1/100,000 wt/vol, and Culex pipiens at 1/10,000 wt/vol in the other. Skin testing of ten volunteers without a history of adverse reactions to mosquito bites was negative. Immunotherapy using these extracts resulted in resolution of adverse reactions to mosquito bites in one patient and a decrease in reactions in the other. Immunotherapy with whole body mosquito extracts is a viable treatment option that can play a role in patients with mosquito bite-induced anaphylaxis. It may also result in severe side effects and one must determine the benefit versus risks for each individual patient.

  10. Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Rachna Raman

    2015-01-01

    Full Text Available Localized renal cell carcinoma (RCC is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

  11. Novel Approaches to Pediatric Cancer: Immunotherapy

    Directory of Open Access Journals (Sweden)

    Payal A. Shah

    2015-06-01

    Full Text Available From the early 20th century, immunotherapy has been studied as a treatment modality for cancers, including in children. Since then, developments in monoclonal antibodies and vaccine therapies have helped to usher in a new era of cancer immunotherapeutics. However, efficacy of these types of therapies has been limited, mostly in part due to low tumor immunogenicity, cancer escape pathways, and toxicities. As researchers investigate the cellular and molecular components of immunotherapies, mechanisms to improve tumor specificity and overcome immune escape have been identified. The goal of immunotherapy now has been to modulate tumor escape pathways while amplifying the immune response by combining innate and adaptive arms of the immune system. Although several limiting factors have been identified, these recent advances in immunotherapy remain at the forefront of pediatric oncologic therapeutic trials. Immunotherapy is now coming to the forefront of precision treatment for a variety of cancers, with evidence that agents targeting immunosuppressive mechanisms for cancer progression can be effective therapy [1-3]. In this review, we review various types of immunotherapy, including the cellular biology, limitations, recent novel therapeutics, and the application of immunotherapy to pediatric oncology.

  12. Improved Endpoints for Cancer Immunotherapy Trials

    Science.gov (United States)

    Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd

    2010-01-01

    Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737

  13. Potentiality of immunotherapy against hepatocellular carcinoma

    Science.gov (United States)

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future. PMID:26420958

  14. IMUNODIAGNOSTIC AND IMMUNOTHERAPY OF AUTISM

    Directory of Open Access Journals (Sweden)

    Vladimir TRAJKOVSKI

    2000-06-01

    Full Text Available Infantile autism is one of the most disabling illnesses of neurological, emotional and intellectual development. The cause of autism remains unknown. However, recent investigations suggest that this disorder shares several features of established autoimmune disorders.The aim of this article is to describe the news of imunodiagnostic and immunotherapy in autism. Interpretation of data is made by conceptual and methodological differences between studies. The autoimmune response is most likely directed against the brain myelin, perhaps secondary to a viral infection. The idea that autism is an autoimmune disorder is further strengthened by the fact that autistic patients respond well to treatment with immune modulating drugs. Immune interventions can produce immune modulation-state of suppression or stimulation. Immune therapy should always be done in consultation with physicians.

  15. [Aβ immunotherapy for Alzheimer's disease].

    Science.gov (United States)

    Sakai, Kenji; Yamada, Masahito

    2013-04-01

    Alzheimer's disease (AD) is one of the neurodegenerative diseases characterized by the deposition of amyloid-β-protein (Aβ) as senile plaques in the brain parenchyma and phosphorylated-tau accumulation as neurofibrillary tangles in the neurons. Although details of the disease pathomechanisms remain unclear, Aβ likely acts as a key protein for AD initiation and progression, followed by abnormal tau phosphorylation and neuronal death (amyloid-cascade hypothesis). According to this hypothesis, Aβ immunization therapies are created to eliminate Aβ from the brain, and to prevent the neurons from damage by these pathogenic proteins. There are two methods for Aβ immunotherapies: active and passive immunization. Previous studies have shown Aβ removal and improved cognitive function in animal models of AD. Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. On the contrary, side effects emerged, such as meningoencephalitis, vasogenic edema, which are currently called amyloid related imaging abnormalities (ARIA)-E and microhemorrhage (ARIA-H). In neuropathological studies of immunized cases, Aβ was removed from the brain parenchyma and phosphorylated-tau was reduced in the neuronal processes. Moreover, deterioration of the cerebral amyloid angiopathy (CAA) and an increase of microhemorrhages and microinfarcts were described. Aβ is cleared from the brain mainly via the lymphatic drainage pathway. ARIA could stem from severe CAA due to dysfunction of the drainage pathway after immunotherapy. Aβ immunization has a potential of cure for AD patients, although the above-described problems must be overcome before applying this therapy in clinical treatment.

  16. Immunological mechanisms of sublingual allergen-specific immunotherapy.

    Science.gov (United States)

    Novak, Natalija; Bieber, T; Allam, J-P

    2011-06-01

    Within the last 100 years of allergen-specific immunotherapy, many clinical and scientific efforts have been made to establish alternative noninvasive allergen application strategies. Thus, intra-oral allergen delivery to the sublingual mucosa has been proven to be safe and effective. As a consequence, to date, sublingual immunotherapy (SLIT) is widely accepted by most allergists as an alternative to conventional subcutaneous immunotherapy. Although immunological mechanisms remain to be elucidated in detail, several studies in mice and humans within recent years provided deeper insights into local as well as systemic immunological features in response to SLIT. First of all, it was shown that the target organ, the oral mucosa, harbours a sophisticated immunological network as an important prerequisite for SLIT, which contains among other cells, local antigen-presenting cells (APC), such as dendritic cells (DCs), with a constitutive disposition to enforce tolerogenic mechanisms. Further on, basic research on local DCs within the oral mucosa gave rise to possible alternative strategies to deliver the allergens to other mucosal regions than sublingual tissue, such as the vestibulum oris. Moreover, characterization of oral DCs led to the identification of target structures for both allergens as well as adjuvants, which could be applied during SLIT. Altogether, SLIT came a long way since its very beginning in the last century and some, but not all questions about SLIT could be answered so far. However, recent research efforts as well as clinical approaches paved the way for another exciting 100 years of SLIT. © 2011 John Wiley & Sons A/S.

  17. Defining the critical hurdles in cancer immunotherapy

    DEFF Research Database (Denmark)

    Fox, Bernard A; Schendel, Dolores J; Butterfield, Lisa H

    2011-01-01

    of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical...... immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation...... companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed...

  18. Allergen immunotherapy for allergic respiratory diseases

    Science.gov (United States)

    Cappella, Antonio; Durham, Stephen R.

    2012-01-01

    Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy. PMID:23095870

  19. Who Will Benefit from Cancer Immunotherapy?

    Science.gov (United States)

    Researchers have identified a “genetic signature” in the tumors of patients with advanced melanoma who responded to a form of immunotherapy called checkpoint blockade. The results could be the basis for a test that identifies likely responders.

  20. Combining Immunotherapy with Standard Glioblastoma Therapy

    Science.gov (United States)

    This clinical trial is testing standard therapy (surgery, radiation and temozolomide) plus immunotherapy with pembrolizumab with or without a cancer treatment vaccine for patients with newly diagnosed glioblastoma, a common and deadly type of brain tumor.

  1. Immunotherapy Combination Approved for Advanced Kidney Cancer

    Science.gov (United States)

    FDA has approved the combination of the immunotherapy drugs nivolumab (Opdivo) and ipilimumab (Yervoy) as an initial treatment for some patients with advanced kidney cancer. The approval is expected to immediately affect patient care, as this Cancer Currents post explains.

  2. PROSTVAC® targeted immunotherapy candidate for prostate cancer.

    Science.gov (United States)

    Shore, Neal D

    2014-01-01

    Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

  3. Mechanisms of Intrinsic Tumor Resistance to Immunotherapy

    Directory of Open Access Journals (Sweden)

    John Rieth

    2018-05-01

    Full Text Available An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO overexpression, loss of phosphatase and tensin homologue (PTEN expression, and overexpression of the Wnt–β-catenin pathway. Current work in immunotherapy continues to identify various tumor resistance mechanisms; future work is needed to develop adjuvant treatments that target those mechanisms, in order to improve the efficacy of immunotherapy and to expand its scope.

  4. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

    2014-01-01

    therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...

  5. Combining radiotherapy and immunotherapy: A revived partnership

    International Nuclear Information System (INIS)

    Demaria, Sandra; Bhardwaj, Nina; McBride, William H.; Formenti, Silvia C.

    2005-01-01

    Ionizing radiation therapy (RT) is an important local modality for the treatment of cancer. The current rationale for its use is based largely on the ability of RT to kill the cancer cells by a direct cytotoxic effect. Nevertheless, considerable evidence indicates that RT effects extend beyond the mere elimination of the more radiosensitive fraction of cancer cells present within a tumor at the time of radiation exposure. For instance, a large body of evidence is accumulating on the ability of RT to modify the tumor microenvironment and generate inflammation. This might have far-reaching consequences regarding the response of a patient to treatment, especially if radiation-induced tumor cell kill were to translate into the generation of effective antitumor immunity. Although much remains to be learned about how radiation can impact tumor immunogenicity, data from preclinical studies provide the proof of principle that different immunotherapeutic strategies can be combined with RT to enhance antitumor effects. Conversely, RT could be a useful tool to combine with immunotherapy. This article will briefly summarize what is known about the impact of RT on tumor immunity, including tumor-associated antigens, antigen-presenting cells, and effector mechanisms. In addition, the experimental evidence supporting the contention that RT can be used as a tool to induce antitumor immunity is discussed, and a new approach to radioimmunotherapy of cancer is proposed

  6. Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project.

    Science.gov (United States)

    Bonertz, A; Roberts, G; Slater, J E; Bridgewater, J; Rabin, R L; Hoefnagel, M; Timon, M; Pini, C; Pfaar, O; Sheikh, A; Ryan, D; Akdis, C; Goldstein, J; Poulsen, L K; van Ree, R; Rhyner, C; Barber, D; Palomares, O; Pawankar, R; Hamerlijnk, D; Klimek, L; Agache, I; Angier, E; Casale, T; Fernandez-Rivas, M; Halken, S; Jutel, M; Lau, S; Pajno, G; Sturm, G; Varga, E M; Gerth van Wijk, R; Bonini, S; Muraro, A; Vieths, S

    2018-04-01

    Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  7. Defining the critical hurdles in cancer immunotherapy

    Science.gov (United States)

    2011-01-01

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571

  8. Defining the critical hurdles in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Fox Bernard A

    2011-12-01

    Full Text Available Abstract Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC, convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

  9. Immunological comparison of allergen immunotherapy tablet treatment and subcutaneous immunotherapy against grass allergy

    DEFF Research Database (Denmark)

    Aasbjerg, K; Backer, V; Lund, G

    2014-01-01

    BACKGROUND: IgE-mediated allergic rhinitis to grass pollen can successfully be treated with either allergen immunotherapy tablets (SLIT tablet) or SQ-standardized subcutaneous immunotherapy (SCIT). The efficacy of these two treatment modalities for grass allergy is comparable, but the immunological...

  10. Accelerated subcutaneous immunotherapy in pediatric population – Systematic review

    Directory of Open Access Journals (Sweden)

    R.A. Gomes dos Reis Pimentel

    2018-05-01

    Full Text Available Background: Accelerated subcutaneous immunotherapy (SCIT schedules represent an alternative to conventional SCIT, providing immunotherapy benefits in a shorter period of time. The objectives of this systematic review were to assess clinical and immunological efficacy as well as safety of accelerated SCIT build-up schedules for the treatment of respiratory allergy in pediatric patients. Methods: Studies were located by searching PubMed, using “immunotherapy” and “desensitization” as keywords. The selection of studies, published from January 1st, 2006, to December 31th, 2015, was performed in two stages: screening of titles and abstracts, and assessment of the full papers identified as relevant, considering the inclusion criteria. Data were extracted in a standardized way and synthesized qualitatively to assess efficacy and safety of accelerated schedules in respiratory allergy. Results: Eleven trials were included: two evaluated rush SCIT and nine assessed cluster SCIT. This review demonstrated that rush and cluster schedules are clinically and immunological efficacious, with faster effect than conventional schedules. No relevant difference with respect to clinical outcomes was noticed between subgroups (pediatric, adult and mixed populations. Regarding safety, most local adverse reactions were mild and there were neither life-threatening systemic reactions nor fatal events. No relevant differences in the incidence and severity of either local or systemic reactions between the accelerated schedule group and control group were registered. Conclusions: Accelerated SCIT build-up schedules are effective in the treatment of respiratory allergy in pediatric patients, representing a safe alternative to the conventional schedules with the advantage of achieving clinical effectiveness sooner. Keywords: Allergy, Immunotherapy, Pediatrics

  11. Particle platforms for cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Serda RE

    2013-04-01

    Full Text Available Rita Elena Serda Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA Abstract: Elevated understanding and respect for the relevance of the immune system in cancer development and therapy has led to increased development of immunotherapeutic regimens that target existing cancer cells and provide long-term immune surveillance and protection from cancer recurrence. This review discusses using particles as immune adjuvants to create vaccines and to augment the anticancer effects of conventional chemotherapeutics. Several particle prototypes are presented, including liposomes, polymer nanoparticles, and porous silicon microparticles, the latter existing as either single- or multiparticle platforms. The benefits of using particles include immune-cell targeting, codelivery of antigens and immunomodulatory agents, and sustained release of the therapeutic payload. Nanotherapeutic-based activation of the immune system is dependent on both intrinsic particle characteristics and on the immunomodulatory cargo, which may include danger signals known as pathogen-associated molecular patterns and cytokines for effector-cell activation. Keywords: adjuvant, particle, immunotherapy, dendritic cell, cancer, vaccine

  12. Dendritic cell-based immunotherapy.

    Science.gov (United States)

    Osada, Takuya; Clay, Timothy M; Woo, Christopher Y; Morse, Michael A; Lyerly, H Kim

    2006-01-01

    Dendritic cells (DCs) play a crucial role in the induction of antigen-specific T-cell responses, and therefore their use for the active immunotherapy of malignancies has been studied with considerable interest. More than a decade has passed since the publication of the first clinical data of DC-based vaccines, and through this and subsequent studies, a number of important developmental insights have been gleaned. These include the ideal source and type of DCs, the discovery of novel antigens and methods of loading DCs, the role of DC maturation, and the most efficient route of immunization. The generation of immune responses against tumor antigens after DC immunization has been demonstrated, and favorable clinical responses have been reported in some patients; however, it is difficult to pool the results as a whole, and thus the body of data remains inconclusive, in part because of varying DC preparation and vaccination protocols, the use of different forms of antigens, and, most importantly, a lack of rigorous criteria for defining clinical responses. As such, the standardization of clinical and immunologic criteria utilized, as well as DC preparations employed, will allow for the comparison of results across multiple clinical studies and is required in order for future trials to measure the true value and role of this treatment modality. In addition, issues regarding the optimal dose and clinical setting for the application of DC vaccines remain to be resolved, and recent clinical studies have been designed to begin to address these questions.

  13. [Specific immunotherapy. Hyposensitization with allergens].

    Science.gov (United States)

    Wedi, B; Kapp, A

    2004-04-01

    Successful allergen-specific immunotherapy (SIT) induces complex immunologic chan-ges resulting in reduced allergic inflammatory reactions. SIT has long-term effects in mild forms of inhalant allergies and is effective even when standard pharmacotherapy fails. Moreover, the risk to develop additional allergic sensitizations and the development of asthma is significantly reduced in children with allergic rhinitis. SIT is the treatment of choice in patients with systemic reactions to hymenoptera venoms. Although the exact effector mechanisms of SIT still have to be clarified, the most probable effect is a modulation of regulatory T cells associated with a switch of allergen-specific B-cells towards IgG4 production. The critical point to insure efficacy and safety is the selection of patients and allergens, task best performed by a specialist trained in allergology. Further details are available in the position papers of the German allergy societies - DGAI(Deutsche Gesellschaft fiir Allergologie und Klinische Immunologie) and ADA (Arzte-verband Deutscher Allergologen) - which can be found at www.dgaki.de.

  14. Development of Artificial Antigen Presenting Cells for Prostate Cancer Immunotherapy

    National Research Council Canada - National Science Library

    Schneck, Jonathan P; Oelke, Mathias

    2007-01-01

    While adoptive immunotherapy holds promise as a treatment for cancer, development of adoptive immunotherapy has been impeded by the lack of a reproducible and economically viable method for generating...

  15. Safety and efficacy of venom immunotherapy: a real life study.

    Science.gov (United States)

    Kołaczek, Agnieszka; Skorupa, Dawid; Antczak-Marczak, Monika; Kuna, Piotr; Kupczyk, Maciej

    2017-04-01

    Venom immunotherapy (VIT) is recommended as the first-line treatment for patients allergic to Hymenoptera venom. To analyze the safety and efficacy of VIT in a real life setting. One hundred and eighty patients undergoing VIT were studied to evaluate the safety, efficacy, incidence and nature of symptoms after field stings and adverse reactions to VIT. Significantly more patients were allergic to wasp than bee venom (146 vs. 34, p bees, and were not associated with angiotensin convertase inhibitors (ACEi) or β-adrenergic antagonists use. Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6 patients allergic to bees (17.65%). The VIT was efficacious as most patients reported no reactions (50%) or reported only mild local reactions (43.75%) to field stings. The decrease in sIgE at completion of VIT correlated with the dose of vaccine received ( r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p venom allergy. Venom immunotherapy is highly efficacious and safe as most of the adverse events during the induction and maintenance phase are mild and local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and female sex are associated with a higher risk of allergy to Hymenoptera venom.

  16. Immune mediated neuropathy following checkpoint immunotherapy.

    Science.gov (United States)

    Gu, Yufan; Menzies, Alexander M; Long, Georgina V; Fernando, S L; Herkes, G

    2017-11-01

    Checkpoint immunotherapy has revolutionised cancer therapy and is now standard treatment for many malignancies including metastatic melanoma. Acute inflammatory neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but potentially severe complication of checkpoint immunotherapy with individual cases described but never characterised as a group. We describe a case of acute sensorimotor and autonomic neuropathy following a single dose of combination ipilimumab and nivolumab for metastatic melanoma. A literature search was performed, identifying 14 other cases of acute neuropathy following checkpoint immunotherapy, with the clinical, electrophysiological and laboratory features summarised. Most cases described an acute sensorimotor neuropathy (92%) with hyporeflexia (92%) that could occur from induction up till many weeks after the final dose of therapy. In contrast to Guillain-Barre syndrome, the cerebrospinal fluid (CSF) analysis often shows a lymphocytic picture (50%) and the electrophysiology showed an axonal pattern (55%). Treatment was variable and often in combination. 11 cases received steroid therapy with only 1 death within this group, whereas of the 4 patients who did not receive steroid therapy there were 3 deaths. In conclusion checkpoint immunotherapy - induced acute neuropathies are distinct from and progress differently to Guillain-Barre syndrome. As with other immunotherapy related adverse events corticosteroid therapy should be initiated in addition to usual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 8

    International Nuclear Information System (INIS)

    Imanaka, Kazufumi; Gose, Kyuhei; Ichiyanagi, Akihiro

    1983-01-01

    The effectiveness of active specific immunotherapy prepared from a low-dose irradiated tumor tissue has already reported. The present study was designed to investigate the effect of Mitomycin C-treated active specific immunotherapy. Twelve-week-aged female C3H/He mice transplanted with MM 46 tumors were exposed to local electron radiotherapy with a dose of 3,000 rad on the 5th day after tumor inoculation. Tumor cells prepared for active specific immunotherapy were pretreated with Mitomycin C at concentration of 20 μg/10 7 cells in Eagle MEM Earle containing 100 IU/ml penicillin. The cell suspension was incubated at 37 0 C for 15 minutes. Mitomycin C-treated active specific immunotherapy was performed on the 12th day. Antitumor effect was evaluated by the regression of the tumor and survival curve. The remarkable regression of the tumor and significant elongation of the survival period were observed in the group which received Mitomycin C-treated active specific immunotherapy and the group which received active specific immunotherapy without the treatment of Mitomycin C. (author)

  18. local

    Directory of Open Access Journals (Sweden)

    Abílio Amiguinho

    2005-01-01

    Full Text Available The process of socio-educational territorialisation in rural contexts is the topic of this text. The theme corresponds to a challenge to address it having as main axis of discussion either the problem of social exclusion or that of local development. The reasons to locate the discussion in this last field of analysis are discussed in the first part of the text. Theoretical and political reasons are there articulated because the question is about projects whose intentions and practices call for the political both in the theoretical debate and in the choices that anticipate intervention. From research conducted for several years, I use contributions that aim at discuss and enlighten how school can be a potential locus of local development. Its identification and recognition as local institution (either because of those that work and live in it or because of those that act in the surrounding context are crucial steps to progressively constitute school as a partner for development. The promotion of the local values and roots, the reconstruction of socio-personal and local identities, the production of sociabilities and the equation and solution of shared problems were the dimensions of a socio-educative intervention, markedly globalising. This scenario, as it is argued, was also, intentionally, one of transformation and of deliberate change of school and of the administration of the educative territoires.

  19. Sublingual immunotherapy (SLIT – indications, mechanism, and efficacy Position paper prepared by the Section of Immunotherapy, Polish Society of Allergy

    Directory of Open Access Journals (Sweden)

    Marek Jutel

    2015-12-01

    Full Text Available SLIT ( sublingual immunotherapy induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy, with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50–100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1 – 3 years has been provided by the large scale double-blind, placebo-controlled (DBPC trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis in both children and adults sensitized to pollen allergens (trees, grass, Parietaria , house dust mites ( Dermatophagoides pteronyssinus, Dermatophagoides farinae , cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 – 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization.

  20. Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Blair, Alex B; Zheng, Lei

    2017-06-01

    The complex interaction between the immune system, the tumor and the microenvironment in pancreatic ductal adenocarcinoma (PDA) leads to the resistance of PDA to immunotherapy. To overcome this resistance, combination immunotherapy is being proposed. However, rational combinations that target multiple aspects of the complex anti-tumor immune response are warranted. Novel clinical trials will investigate and optimize the combination immunotherapy for PDA.

  1. Immunotherapy in prostate cancer: challenges and opportunities.

    Science.gov (United States)

    Noguchi, Masanori; Koga, Noriko; Moriya, Fukuko; Itoh, Kyogo

    2016-01-01

    Although treatment options for castration-resistant prostate cancer (CRPC) have increased over the last decade, there remains a need for strategies that can provide durable disease control and long-term benefit. Recently, immunotherapy has emerged as a viable and attractive strategy for the treatment of CRPC. To date, there are multiple strategies to target the immune system, and several approaches including therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in clinical trials. With regard to this, we report the results of the most recent clinical trials investigating immunotherapy in CRPC and discuss the future development of immunotherapy for CRPC, as well as the potential importance of biomarkers in the future progress of this field.

  2. Development of Novel Immunotherapies for Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Ensaf M. Al-Hujaily

    2016-09-01

    Full Text Available Multiple myeloma (MM is a disorder of terminally differentiated plasma cells characterized by clonal expansion in the bone marrow (BM. It is the second-most common hematologic malignancy. Despite significant advances in therapeutic strategies, MM remains a predominantly incurable disease emphasizing the need for the development of new treatment regimens. Immunotherapy is a promising treatment modality to circumvent challenges in the management of MM. Many novel immunotherapy strategies, such as adoptive cell therapy and monoclonal antibodies, are currently under investigation in clinical trials, with some already demonstrating a positive impact on patient survival. In this review, we will summarize the current standards of care and discuss major new approaches in immunotherapy for MM.

  3. Anti-CD40-mediated cancer immunotherapy

    DEFF Research Database (Denmark)

    Hassan, Sufia Butt; Sørensen, Jesper Freddie; Olsen, Barbara Nicola

    2014-01-01

    activation and thus enhancement of immune responses. Treatment with anti-CD40 monoclonal antibodies has been exploited in several cancer immunotherapy studies in mice and led to the development of anti-CD40 antibodies for clinical use. Here, Dacetuzumab and Lucatumumab are in the most advanced stage...... with other cancer immunotherapies, in particular interleukin (IL)-2. An in-depth analysis of this immunotherapy is provided elsewhere. In the present review, we provide an update of the most recent clinical trials with anti-CD40 antibodies. We present and discuss recent and ongoing clinical trials...... in this field, including clinical studies which combine anti-CD40 treatment with other cancer-treatments, such as Rituximab and Tremelimumab....

  4. Immunotherapy in allergy and cellular tests

    Science.gov (United States)

    Chirumbolo, Salvatore

    2014-01-01

    The basophil activation test (BAT) is an in vitro assay where the activation of basophils upon exposure to various IgE-challenging molecules is measured by flow cytometry. It is a cellular test able to investigate basophil behavior during allergy and allergy immunotherapy. A panoply of critical issues and suggestive advances have rendered this assay a promising yet puzzling tool to endeavor a full comprehension of innate immunity of allergy desensitization and manage allergen or monoclonal anti-IgE therapy. In this review a brief state of art of BAT in immunotherapy is described focusing onto the analytical issue pertaining BAT performance in allergy specific therapy. PMID:24717453

  5. Immunotherapy for advanced melanoma: future directions.

    Science.gov (United States)

    Valpione, Sara; Campana, Luca G

    2016-02-01

    As calculated by the meta-analysis of Korn et al., the prognosis of metastatic melanoma in the pretarget and immunological therapy era was poor, with a median survival of 6.2 and a 1-year life expectancy of 25.5%. Nowadays, significant advances in melanoma treatment have been gained, and immunotherapy is one of the promising approaches to get to durable responses and survival improvement. The aim of the present review is to highlight the recent innovations in melanoma immunotherapy and to propose a critical perspective of the future directions of this enthralling oncology subspecialty.

  6. Antigen Presentation Keeps Trending in Immunotherapy Resistance.

    Science.gov (United States)

    Kalbasi, Anusha; Ribas, Antoni

    2018-04-19

    Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T-cell immunotherapy not previously identified using CRISPR-based screens. MEX3B is a posttranscriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T-cell immunotherapy and indicating a new putative molecular target. Clin Cancer Res; 24(14); 1-3. ©2018 AACR. See related article by Huang et al., p. xxxx . ©2018 American Association for Cancer Research.

  7. Tinnitus after administration of sublingual immunotherapy

    DEFF Research Database (Denmark)

    Juel, Jacob

    2017-01-01

    , for example, itching, swelling, irritation, ulceration of the oropharynx and nausea, abdominal pain, diarrhoea, and vomiting. More severe side effects are dominated by systemic and respiratory tract manifestations. RESULTS: In this clinical case, the author reports a right-sided transient tinnitus lasting...... for 48 h after administration of sublingual immunotherapy for house dust mite in allergic rhinitis. CONCLUSIONS: This case provide important insights for clinical practice, as tinnitus has not been previously reported as a side effect of sublingual immunotherapy with house dust mite allergens....

  8. Immunotherapy (oral and sublingual) for food allergy to fruits.

    Science.gov (United States)

    Yepes-Nuñez, Juan Jose; Zhang, Yuan; Roqué i Figuls, Marta; Bartra Tomas, Joan; Reyes, Juan Manuel; Pineda de la Losa, Fernando; Enrique, Ernesto

    2015-11-09

    Food allergy is an abnormal immunological response following exposure (usually ingestion) to a food. Elimination of the allergen is the principle treatment for food allergy, including allergy to fruit. Accidental ingestion of allergenic foods can result in severe anaphylactic reactions. Allergen-specific immunotherapy (SIT) is a specific treatment, when the avoidance of allergenic foods is problematic. Recently, studies have been conducted on different types of immunotherapy for the treatment of food allergy, including oral (OIT) and sublingual immunotherapy (SLIT). To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits, when compared with placebo or an elimination strategy. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and AMED were searched for published results along with trial registries and the Journal of Negative Results in BioMedicine for grey literature. The date of the most recent search was July 2015. Randomised controlled trials (RCTs) comparing OIT or SLIT with placebo or an elimination diet were included. Participants were children or adults diagnosed with food allergy who presented immediate fruit reactions. We used standard methodological procedures expected by the Cochrane Collaboration. We assessed treatment effect through risk ratios (RRs) for dichotomous outcomes. We identified two RCTs (N=89) eligible for inclusion. These RCTs addressed oral or sublingual immunotherapy, both in adults, with an allergy to apple or peach respectively. Both studies enrolled a small number of participants and used different methods to provide these differing types of immunotherapy. Both studies were judged to be at high risk of bias in at least one domain. Overall, the quality of evidence was judged to be very low due to the small number of studies and participants and possible bias. The studies were clinically heterogeneous and hence we did not pool the

  9. Novel immunotherapy and treatment modality for severe food allergies.

    Science.gov (United States)

    Nagakura, Ken-Ichi; Sato, Sakura; Yanagida, Noriyuki; Ebisawa, Motohiro

    2017-06-01

    In recent years, many studies on oral immunotherapy (OIT) have been conducted; however, few have focused on severe food allergies. The purpose of this review was to assess the efficacy and safety of oral immunotherapies for patients with severe food allergy. We reviewed multiple immunotherapy reports published within a few years or reports focusing on severe food allergies. We also investigated recent studies on OIT and novel food allergy management. Immunotherapies targeting low-dose antigen exposure and oral food challenges using low-dose target volumes may be safer than conventional OIT. It is necessary to consider which immunotherapy regimen is appropriate based on allergy severity of the patient.

  10. Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma.

    Science.gov (United States)

    Rini, Brian I; McDermott, David F; Hammers, Hans; Bro, William; Bukowski, Ronald M; Faba, Bernard; Faba, Jo; Figlin, Robert A; Hutson, Thomas; Jonasch, Eric; Joseph, Richard W; Leibovich, Bradley C; Olencki, Thomas; Pantuck, Allan J; Quinn, David I; Seery, Virginia; Voss, Martin H; Wood, Christopher G; Wood, Laura S; Atkins, Michael B

    2016-01-01

    Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR). Additionally, a new class of immunotherapy agents, immune checkpoint inhibitors, is emerging and will play a significant role in the treatment of patients with RCC. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a Task Force, which met to consider the current role of approved immunotherapy agents in RCC, to provide guidance to practicing clinicians by developing consensus recommendations and to set the stage for future immunotherapeutic developments in RCC.

  11. Use of lectin-functionalized particles for oral immunotherapy

    Science.gov (United States)

    Diesner, Susanne C; Wang, Xue-Yan; Jensen-Jarolim, Erika; Untersmayr, Eva; Gabor, Franz

    2013-01-01

    Immunotherapy, in recent times, has found its application in a variety of immunologically mediated diseases. Oral immunotherapy may not only increase patient compliance but may, in particular, also induce both systemic as well as mucosal immune responses, due to mucosal application of active agents. To improve the bioavailability and to trigger strong immunological responses, recent research projects focused on the encapsulation of drugs and antigens into polymer particles. These particles protect the loaded antigen from the harsh conditions in the GI tract. Furthermore, modification of the surface of particles by the use of lectins, such as Aleuria aurantia lectin, wheatgerm agglutinin or Ulex europaeus-I, enhances the binding to epithelial cells, in particular to membranous cells, of the mucosa-associated lymphoid tissue. Membranous cell-specific targeting leads to an improved transepithelial transport of the particle carriers. Thus, enhanced uptake and presentation of the encapsulated antigen by antigen-presenting cells favor strong systemic, but also local, mucosal immune responses. PMID:22834202

  12. Biomarkers and correlative endpoints for immunotherapy trials.

    Science.gov (United States)

    Morse, Michael A; Osada, Takuya; Hobeika, Amy; Patel, Sandip; Lyerly, H Kim

    2013-01-01

    Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer.

  13. Targeting nanoparticles to dendritic cells for immunotherapy.

    NARCIS (Netherlands)

    Cruz, L.J.; Tacken, P.J.; Rueda, F.; Domingo, J.C.; Albericio, F.; Figdor, C.G.

    2012-01-01

    Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy for treatment of cancer and infectious diseases. Development of targeted nanodelivery systems carrying vaccine components, including antigens and adjuvants, to DCs in

  14. Novel immunotherapy approaches to food allergy

    NARCIS (Netherlands)

    Hayen, Simone M; Kostadinova, Atanaska I; Garssen, Johan; Otten, Henny G; Willemsen, Linette E M

    2014-01-01

    PURPOSE OF REVIEW: Despite reaching high percentages of desensitization using allergen-specific immunotherapy (SIT) in patients with food allergy, recent studies suggest only a low number of patients to reach persistent clinical tolerance. This review describes current developments in strategies to

  15. Cancer immunotherapy : insights from transgenic animal models

    NARCIS (Netherlands)

    McLaughlin, PMJ; Kroesen, BJ; Harmsen, MC; de Leij, LFMH

    2001-01-01

    A wide range of strategies in cancer immunotherapy has been developed in the last decade, some of which are currently being used in clinical settings. The development of these immunotherapeutical strategies has been facilitated by the generation of relevant transgenic animal models. Since the

  16. Steroids vs immunotherapy for allergic rhinitis

    DEFF Research Database (Denmark)

    Aasbjerg, Kristian; Backer, Vibeke

    2014-01-01

    Treatment for seasonal allergic rhinitis induced by airborne allergens can be divided into two major groups: symptom-dampening drugs, such as antihistamines and corticosteroids, and disease-modifying drugs in the form of immunotherapy. It has been speculated that depot-injection corticosteroids g...

  17. Proceedings of the 2016 China Cancer Immunotherapy Workshop

    Directory of Open Access Journals (Sweden)

    Bin Xue

    2016-10-01

    Full Text Available Table of contents A1 Proceedings of 2016 China Cancer Immunotherapy Workshop, Beijing, China Bin Xue, Jiaqi Xu, Wenru Song, Zhimin Yang, Ke Liu, Zihai Li A2 Set the stage: fundamental immunology in forty minutes Zihai Li A3 What have we learnt from the anti-PD-1/PD-L1 therapy of advanced human cancer? Lieping Chen A4 Immune checkpoint inhibitors in lung cancer Edward B. Garon A5 Mechanisms of response and resistance to checkpoint inhibitors in melanoma Siwen Hu-Lieskovan A6 Checkpoint inhibitor immunotherapy in lymphoid malignancies Wei Ding A7 Translational research to improve the efficacy of immunotherapy in genitourinary malignancies Chong-Xian Pan A8 Immune checkpoint inhibitors in gastrointestinal malignancies Weijing Sun A9 What’s next beyond PD-1/PDL1? Yong-Jun Liu A10 Cancer vaccines: new insights into the oldest immunotherapy strategy Lei Zheng A11 Bispecific antibodies for cancer immunotherapy Delong Liu A12 Updates on CAR-T immunotherapy Michel Sadelain A13 Adoptive T cell therapy: personalizing cancer treatment Cassian Yee A14 Immune targets and neoantigens for cancer immunotherapy Rongfu Wang A15 Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with advanced and metastatic solid tumors Meixia Chen, Yao Wang, Zhiqiang Wu, Hanren Dai, Can Luo, Yang Liu, Chuan Tong, Yelei Guo, Qingming Yang, Weidong Han A16 Cancer immunotherapy biomarkers: progress and issues Lisa H. Butterfield A17 Shaping of immunotherapy response by cancer genomes Timothy A. Chan A18 Unique development consideration for cancer immunotherapy Wenru Song A19 Immunotherapy combination Ruirong Yuan A20 Immunotherapy combination with radiotherapy Bo Lu A21 Cancer immunotherapy: past, present and future Ke Liu A22 Breakthrough therapy designation drug development and approval Max Ning A23 Current European regulation of innovative oncology medicines: opportunities for immunotherapy Harald Enzmann, Heinz Zwierzina

  18. Amyloid beta peptide immunotherapy in Alzheimer disease.

    Science.gov (United States)

    Delrieu, J; Ousset, P J; Voisin, T; Vellas, B

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome

    Directory of Open Access Journals (Sweden)

    Tae Beom Kim, MD, PhD

    2018-06-01

    Full Text Available Post-orgasmic illness syndrome (POIS is a very rare disease characterized by local allergic symptoms and transient flu-like illness that nearly always occur after masturbation, coitus, or spontaneous ejaculation and last for 2 to 7 days. In a previous case report, 2 patients with POIS received hyposensitization therapy composed of multiple subcutaneous injections of autologous semen that resulted in a gradual decrease of symptoms. However, this procedure requires patients to endure pain and discomfort during frequent subcutaneous injections and preceding masturbations to obtain the autologous semen used for therapy. Recent studies have suggested that intralymphatic immunotherapy is a promising new method of allergen-specific immunotherapy against allergic diseases, showing a faster onset and longer duration of therapeutic effects after only several intralymphatic injections. We report on a case of a Korean man with POIS who received intralymphatic immunotherapy that alleviated POIS-related symptoms and in whom the existence of semen-specific immunoglobulin E was confirmed using immunoglobulin E immunoblotting and enzyme-linked immunosorbent assay.Kim TB, Shim YS, Lee, SM, et al. Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome. Sex Med 2018;6:174–179. Key Words: Post-Orgasmic illness, Injection, Intralymphatic, Desensitization, Immunologic, Semen

  20. Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

    International Nuclear Information System (INIS)

    Wada, Satoshi; Harris, Timothy J.; Tryggestad, Erik; Yoshimura, Kiyoshi; Zeng, Jing; Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C.; De Marzo, Angelo M.

    2013-01-01

    Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting

  1. Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Satoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Harris, Timothy J.; Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yoshimura, Kiyoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C. [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); De Marzo, Angelo M. [Department of Pathology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); and others

    2013-11-15

    Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.

  2. Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome.

    Science.gov (United States)

    Kim, Tae Beom; Shim, Young Sup; Lee, Sang Min; Son, Eun Suk; Shim, Jung Woo; Lee, Sang Pyo

    2018-06-01

    Post-orgasmic illness syndrome (POIS) is a very rare disease characterized by local allergic symptoms and transient flu-like illness that nearly always occur after masturbation, coitus, or spontaneous ejaculation and last for 2 to 7 days. In a previous case report, 2 patients with POIS received hyposensitization therapy composed of multiple subcutaneous injections of autologous semen that resulted in a gradual decrease of symptoms. However, this procedure requires patients to endure pain and discomfort during frequent subcutaneous injections and preceding masturbations to obtain the autologous semen used for therapy. Recent studies have suggested that intralymphatic immunotherapy is a promising new method of allergen-specific immunotherapy against allergic diseases, showing a faster onset and longer duration of therapeutic effects after only several intralymphatic injections. We report on a case of a Korean man with POIS who received intralymphatic immunotherapy that alleviated POIS-related symptoms and in whom the existence of semen-specific immunoglobulin E was confirmed using immunoglobulin E immunoblotting and enzyme-linked immunosorbent assay. Kim TB, Shim YS, Lee, SM, et al. Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome. Sex Med 2018;6:174-179. Copyright © 2018. Published by Elsevier Inc.

  3. Allergen-specific immunotherapy of Hymenoptera venom allergy

    DEFF Research Database (Denmark)

    Schiener, Maximilian; Graessel, Anke; Ollert, Markus

    2017-01-01

    Stings of hymenoptera can induce IgE-mediated hypersensitivity reactions in venom-allergic patients, ranging from local up to severe systemic reactions and even fatal anaphylaxis. Allergic patients' quality of life can be mainly improved by altering their immune response to tolerate the venoms...... by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy......, but was additionally used to create tools which enable the analysis of therapeutic venom extracts on a molecular level. Therefore, during the last decade the detailed knowledge of the allergen composition of hymenoptera venoms has substantially improved diagnosis and therapy of venom allergy. This review focuses...

  4. Allergen immunotherapy for IgE-mediated food allergy

    DEFF Research Database (Denmark)

    Nurmatov, Ulugbek; Dhami, S; Arasi, S.

    2017-01-01

    Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness...... economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic...... adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT....

  5. Lactococcus lactis As a Versatile Vehicle for Tolerogenic Immunotherapy

    Science.gov (United States)

    Cook, Dana P.; Gysemans, Conny; Mathieu, Chantal

    2018-01-01

    Genetically modified Lactococcus lactis bacteria have been engineered as a tool to deliver bioactive proteins to mucosal tissues as a means to exert both local and systemic effects. They have an excellent safety profile, the result of years of human consumption in the food industry, as well as a lack of toxicity and immunogenicity. Also, containment strategies have been developed to promote further application as clinical protein-based therapeutics. Here, we review technological advancements made to enhanced the potential of L. lactis as live biofactories and discuss some examples of tolerogenic immunotherapies mediated by mucosal drug delivery via L. lactis. Additionally, we highlight their use to induce mucosal tolerance by targeted autoantigen delivery to the intestine as an approach to reverse autoimmune type 1 diabetes. PMID:29387056

  6. Immunotherapy: A breakthrough in cancer research

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2016-12-01

    Full Text Available The fast growing field of immunotherapy was one of the topics extensively discussed during the recently concluded ESMO Asia Congress 2016, held from December 16– 19th December at the Suntec Convention and Exhibition Centre in Singapore. Unlike drug-based chemotherapy, immunotherapy exploits the body’s own immune system to fight cancer and is increasingly touted as the future of cancer treatment. The concept of using the immune system as a disease-fighting tool was introduced by Dr. William Bradley Coley, the ‘Father of Cancer Immunotherapy’, in the 19th century based on his work that sought to stimulate a patient’s own immune system against bacterial infection. However, a persistent question remains since the advent of immunotherapy over a century ago – can the immune system accurately recognize malignant tumor and eliminate it effectively? The answer to this question remains hotly debated owing to the differing opinions and attitudes on the application of immunotherapy. Dr. Coley noticed that in a number of cases, patients with cancer went into spontaneous remission after developing erysipelas. In 1891, Dr. Coley injected streptococcal organisms (which cause erysipelas into a patient with inoperable cancer and observed remarkable tumor regression. Although he had treated almost 900 patients with bacterial preparations that eventually became known as “Coley’s toxins”, his treatment method was not widely accepted by the medical community possibly owing to the low cure rates and the severe fever caused by the bacteria. Some physicians also feared that the immune system might not have adapted well enough to recognize and eliminate malignant cells exclusively. As a consequence, most oncologists relied on another treatment that was rapidly gaining acceptance at that time, i.e. radiation. It was only after about a century later that the medical community observed a revived interest in immunotherapy. In 1976, a trial was conducted to

  7. Interstitial laser immunotherapy for treatment of metastatic mammary tumors in rats

    Science.gov (United States)

    Figueroa, Daniel; Joshi, Chet; Wolf, Roman F.; Walla, Jonny; Goddard, Jessica; Martin, Mallory; Kosanke, Stanley D.; Broach, Fred S.; Pontius, Sean; Brown, Destiny; Li, Xiaosong; Howard, Eric; Nordquist, Robert E.; Hode, Tomas; Chen, Wei R.

    2011-03-01

    Thermal therapy has been used for cancer treatment for more than a century. While thermal effect can be direct, immediate, and controllable, it is not sufficient to completely eradicate tumors, particularly when tumors have metastasized locally or to the distant sites. Metastases are the major cause of treatment failure and cancer deaths. Current available therapies, such as surgery, radiation, and chemotherapy, only have limited curative effects in patients with late-stage, metastatic cancers. Immunotherapy has been considered as the ultimate approach for cancer treatment since a systemic, anti-tumor, immunological response can be induced. Using the combination of photothermal therapy and immunotherapy, laser immunotherapy (LIT),a novel immunotherapy modality for late-stage cancer treatment, has been developed. LIT has shown great promise in pre-clinical studies and clinical breast cancer and melanoma pilot trials. However, the skin color and the depth of the tumor have been challenges for effective treatment with LIT. To induce a thermal destruction zone of appropriate size without causing thermal damage on the skin, we have developed interstitial laser immunotherapy (ILIT) using a cylindrical diffuser. To determine the effectiveness of ILIT, we treated the DMBA-4 metastatic tumors in rats. The thermal damage in tumor tissue was studied using TTC immersion and hematoxolin and eosin (H & E) staining. Also observed was the overall survival of the treated animals. Our results demonstrated that the ILIT could impact a much larger tumor area, and it significantly reduced the surface damage compared with the early version of non-invasive LIT. The survival data also indicate that ILIT has the potential to become an effective tool for the treatment of deeper, larger, and metastatic tumors, with reduced side effects.

  8. Advances of Immunotherapy in Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jingjing LIU

    2014-06-01

    Full Text Available Small cell lung cancer (SCLC is complex heterogeneous due to unclear biological characteristics in terms of cell origin, pathogenesis and driver genes etc. Diagnosis and treatment of SCLC has been slowly improved and few breakthroughs have been discovered up to now. Therefore new strategies are urgently needed to improve the efficacy of SCLC treatment. Tumor immunotherapy has potential to restore and trigger the immune system to recognize and eliminate tumor cells, notably it has only minimal adverse impact on normal tissue. Cancer vaccine, adoptive immunotherapy, cytokines and checkpoint inhibitors have now been launched for clinical treatment of SCLC. Ipilimumab is the most promising medicine of immunotherapy. Immunotherapy is expected to bring new vision to the treatment of SCLC. And further researches are needed on such problems affecting efficacy of immunotherapy as the heterogeneity of SCLC, the uncertainty of target for immunotherapy, the immune tolerance, etc.

  9. Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen

    DEFF Research Database (Denmark)

    Aliu, Have; Rask, Carola; Brimnes, Jens

    2017-01-01

    Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the - treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development...

  10. Efficacy of Mycobacterium indicus pranii immunotherapy as an adjunct to chemotherapy for tuberculosis and underlying immune responses in the lung.

    Directory of Open Access Journals (Sweden)

    Ankan Gupta

    Full Text Available BACKGROUND: The 9-month-long chemotherapy of tuberculosis often results in poor compliance and emergence of drug-resistant strains. So, improved therapeutic strategy is urgently needed. Immunotherapy could be beneficial for the effective management of the disease. Previously we showed the protective efficacy of Mycobacterium indicus pranii (MIP when given as prophylactic vaccine in animal models of tuberculosis. METHODS: We sought to investigate whether MIP can be used as an adjunct to the chemotherapy in guinea pig models of tuberculosis. Efficacy of MIP was evaluated when given subcutaneously or by aerosol. RESULTS: MIP-therapy as an adjunct to the chemotherapy was found to be effective in accelerating bacterial killing and improving organ pathology. MIP-immunotherapy resulted in higher numbers of activated antigen-presenting cells and lymphocytes in the infected lungs and also modulated the granulomatous response. Early increase in protective Th1 immune response was observed in the immunotherapy group. Following subsequent doses of MIP, decrease in the inflammatory response and increase in the immunosuppressive response was observed, which resulted in the improvement of lung pathology. CONCLUSION: MIP immunotherapy is a valuable adjunct to chemotherapy for tuberculosis. Aerosol route of immunotherapy can play a crucial role for inducing immediate local immune response in the lung.

  11. Next generation immunotherapy for tree pollen allergies.

    Science.gov (United States)

    Su, Yan; Romeu-Bonilla, Eliezer; Heiland, Teri

    2017-10-03

    Tree pollen induced allergies are one of the major medical and public health burdens in the industrialized world. Allergen-Specific Immunotherapy (AIT) through subcutaneous injection or sublingual delivery is the only approved therapy with curative potential to pollen induced allergies. AIT often is associated with severe side effects and requires long-term treatment. Safer, more effective and convenient allergen specific immunotherapies remain an unmet need. In this review article, we discuss the current progress in applying protein and peptide-based approaches and DNA vaccines to the clinical challenges posed by tree pollen allergies through the lens of preclinical animal models and clinical trials, with an emphasis on the birch and Japanese red cedar pollen induced allergies.

  12. Immunotherapy of Human Papilloma Virus Induced Disease

    Science.gov (United States)

    van der Burg, Sjoerd H

    2012-01-01

    Immunotherapy is the generic name for treatment modalities aiming to reinforce the immune system against diseases in which the immune system plays a role. The design of an optimal immunotherapeutic treatment against chronic viruses and associated diseases requires a detailed understanding of the interactions between the target virus and its host, in order to define the specific strategies that may have the best chance to deliver success at each stage of disease. Recently, a first series of successes was reported for the immunotherapy of Human Papilloma Virus (HPV)-induced premalignant diseases but there is definitely room for improvement. Here I discuss a number of topics that in my opinion require more study as the answers to these questions allows us to better understand the underlying mechanisms of disease and as such to tailor treatment. PMID:23341861

  13. Immunotherapy in the management of sepsis.

    Science.gov (United States)

    Sikora, Janusz Piotr

    2002-01-01

    This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.

  14. Should we encourage allergen immunotherapy during pregnancy?

    Science.gov (United States)

    Lieberman, Jay

    2014-03-01

    Primary prevention of allergy is a laudable goal, but one that has unfortunately proven difficult to achieve. Many different strategies have been reported to date, but unequivocal supporting data for any single strategy does not exist. Any successful strategy must lead to immunomodulation and must be encountered very early on life, likely in utero. Reports of early bacterial and farm animal exposures lend supportive data to the concept of immune regulation via early fetal exposure, howeve attempts at clinical applications of this, such as probiotics has not been completely successful. One practical, clinical method for achieving a similar immune modulation to these exposures would be providing atopic women with allergy immunotherapy while pregnant (or perhaps even preconception). Allergy immunotherapy is associated with favorable immune modulation and some data suggest that these changes if produced in mother can influence the atopic status of offspring.

  15. RNA-Based Vaccines in Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Megan A. McNamara

    2015-01-01

    Full Text Available RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

  16. Malignant mesothelioma clinical trial combines immunotherapy drugs.

    Science.gov (United States)

    Chatwal, Monica S; Tanvetyanon, Tawee

    2018-04-01

    Immunotherapy by checkpoint inhibitor is effective for a number of solid tumors including malignant mesothelioma. Studies utilizing single-agent PD-1 or PD-L1 inhibitor for mesothelioma have reported tumor response rates in approximately 10-20% of patients treated. Given the success of combining these agents with CTLA-4 inhibitor in melanoma, there is a strong rationale to study it in mesothelioma. Recently results from clinical trials investigating this approach have been released. Though limited by small sample size, the studies conclusively demonstrated feasibility and suggested a modestly higher tumor response rate than one would expect from treatment with single-agent PD-1 or PD-L1 inhibitor. Nevertheless, toxicity was also increased. Immunotherapy-related deaths due to encephalitis, renal failure and hepatitis were observed. Further studies are warranted.

  17. Splenectomy combined with gastrectomy and immunotherapy for advanced gastric cancer.

    Science.gov (United States)

    Miwa, H; Orita, K

    1983-06-01

    We studied the effects of a splenectomy in combination with immunotherapy on the survival of patients who had undergone a total gastrectomy. It was found that a splenectomy was not effective against advanced gastric cancer at stage III, and that the spleen should be retained for immunotherapy. Splenectomy for gastric cancer at terminal stage IV, particularly in combination with immunotherapy, produced not only augmentation of cellular immunity, but also increased survival.

  18. Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0260 TITLE: Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets PRINCIPAL INVESTIGATOR: Carla Kim... Cell Carcinoma Stem Cells as Immunotherapy Targets 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0260 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new

  19. CDK5 A Novel Role in Prostate Cancer Immunotherapy

    Science.gov (United States)

    2016-10-01

    Parallel: No scientific or budgetary overlap 90091646 (PI: Drake) Title: Enhancing Prostate Cancer Immunotherapy through Epigenetic Reprogramming for...Enhancing Prostate Cancer Immunotherapy through Epigenetic Reprogramming for Optimal Activation of Specific Effector T-Cells Time commitment: 1.2 calendar...AWARD NUMBER: W81XWH-15-1-0670 TITLE: CDK5-A Novel Role in Prostate Cancer Immunotherapy PRINCIPAL INVESTIGATOR: Dr. Barry Nelkin

  20. Combination of omalizumab and bee venom immunotherapy: does it work?

    Science.gov (United States)

    Yılmaz, İnsu; Bahçecioğlu, Sakine Nazik; Türk, Murat

    2018-01-01

    Bee venom immunotherapy (b-VIT) can be combined with omalizumab therapy in order to suppress systemic reactions developing due to b-VIT itself. Omalizumab acts as a premedication and gains time for the immunotherapy to develop its immunomodulatory effects. However, the combination of omalizumab and b-VIT is not always effective enough. Herein we present a patient in whom successful immunotherapy cannot be achieved with combination of omalizumab to b-VIT.

  1. Immunotherapy for the Treatment of Glioblastoma

    Science.gov (United States)

    Thomas, Alissa A.; Ernstoff, Marc S.; Fadul, Camilo E.

    2012-01-01

    Glioblastoma, the most aggressive primary brain tumor, thrives in a microenvironment of relative immunosuppression within the relatively immune-privileged central nervous system. Despite treatments with surgery, radiation therapy, and chemotherapy, prognosis remains poor. The recent success of immunotherapy in the treatment of other cancers has renewed interest in vaccine therapy for the treatment of gliomas. In this article, we outline various immunotherapeutic strategies, review recent clinical trials data, and discuss the future of vaccine therapy for glioblastoma. PMID:22290259

  2. MBCP - Approach - Immunotherapy | Center for Cancer Research

    Science.gov (United States)

    Immunotherapy CCR investigators pioneered the use of the tuberculosis vaccine—Bacillus Calmette-Guerin (BCG)—in the treatment of bladder cancer. In cases where the tumor burden is not too high and direct contact can be made with the urothelium surface of the bladder, BCG application appears to elicit an immune response that attacks the tumor as well as the attenuated virus.

  3. ATMPs for Cancer Immunotherapy: A Regulatory Overview.

    Science.gov (United States)

    Galli, Maria Cristina

    2016-01-01

    This chapter discusses European regulatory requirements for development of advanced therapy medicinal products (ATMP) for cancer immunotherapy approaches, describing the framework for clinical trials and for marketing authorization.Regulatory critical issues and challenges for developing ATMP are also discussed, with focus on potency determination, long-term follow-up, comparability, and insertional mutagenesis issues. Some of the most critical features of GMP application to ATMP are also described.

  4. Immunotherapy with the storage mite lepidoglyphus destructor.

    Science.gov (United States)

    Armentia-Medina, A; Tapias, J A; Martín, J F; Ventas, P; Fernández, A

    1995-01-01

    We carried out a double-blind clinical trial of immunotherapy on 35 patients sensitized to the storage mite Lepidoglyphus destructor (Ld). Before and after 12 months of specific hyposensitization (Abelló Lab., Spain) we performed in vivo (skin tests with Ld, methacholine and challenge tests), and in vitro tests (specific IgE, IgG, IgG1 and IgG4 to Ld and specific IgE, IgG, IgG1 and IgG4 to their major allergen Lep dI). We also monitored the efficacy and safety of the immunotherapy with clinical and analytical controls (symptoms and medication score, detection of immune complexes). After therapy we found a significant decrease in specific skin reactivity, dose of positive challenge tests, and hyperresponsiveness to methacholine. Sputum eosinophilia decreased. Specific IgE to Ld was increased and we also observed an increase in specific IgG1 and IgG4 to Ld and Lep DI. The placebo group showed no changes in these variables. There were no severe secondary reactions after treatment with the extract. Patients-self-evaluation was favourable and their labour absence decreased. No development of circulating immune complexes was associated with this immunotherapy.

  5. Assessing the efficacy of immunotherapy with a glutaraldehyde-modified house dust mite extract in children by monitoring changes in clinical parameters and inflammatory markers in exhaled breath.

    Science.gov (United States)

    Lozano, Jaime; Cruz, María-Jesús; Piquer, Mónica; Giner, Maria-Teresa; Plaza, Ana María

    2014-01-01

    The aim of this study was to evaluate the effectiveness of specific immunotherapy (SIT) management with allergoids in children with allergic asthma by monitoring changes in clinical parameters and inflammatory markers in exhaled breath. The study population included 43 patients (24 males) of 6-14 years of age, who had allergic asthma and were sensitized to mites. Twenty-three individuals were treated with subcutaneous SIT (PURETHAL® Mites, HAL Allergy) for 8 months, i.e. the SIT group, and 20 were given medication to treat symptoms only, i.e. the control group. Before treatment and after 4 and 8 months, several clinical parameters, the levels of exhaled nitric oxide and the pH of exhaled breath condensate (EBC) were determined. The SIT group presented with an improvement in asthma classification, a reduction in maintenance drug therapy and improved scores on the quality-of-life questionnaire. These changes were not observed in the control group. Both groups presented significant decreases in EBC pH values at 4 and 8 months after treatment compared to at baseline. However, analysis of the variable 'ratio' showed an increase in the EBC pH values after 8 months of treatment in the SIT group compared with the values at 4 months. SIT with standardized mite extract reduces asthma symptoms in children. A decrease in EBC pH values was observed in both groups, although the SIT group presented a tendency of recovered values after 8 months. Future studies of EBC pH monitoring in the longer term are needed to determine the effectiveness of this marker. © 2014 S. Karger AG, Basel.

  6. EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Calderon Moises A

    2012-10-01

    Full Text Available Abstract Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy. Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies. Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals’ quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases. Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in

  7. Stinging insect allergy: current perspectives on venom immunotherapy

    Directory of Open Access Journals (Sweden)

    Ludman SW

    2015-07-01

    Full Text Available Sian W Ludman,1 Robert J Boyle2 1Paediatric Allergy Department, St Mary's Hospital, Imperial Healthcare NHS Trust, London, UK; 2Department of Paediatrics, Imperial College London, London, UKAbstract: Systemic allergic reactions to insect stings affect up to 5% of the population during their lifetime, and up to 32% of beekeepers. Such reactions can be fatal, albeit very rarely, and fear of a further systemic reaction (SR can lead to significant anxiety and quality of life impairment. A recent Cochrane systematic review confirmed that venom immunotherapy (VIT is an effective treatment for people who have had a systemic allergic reaction to an insect sting. VIT reduces risk of a further SR (relative risk 0.10, 95% confidence interval 0.03–0.28, but VIT also reduces risk of a future large local reaction, and significantly improves disease-specific quality of life. However, health economic analysis showed that VIT is generally not cost effective for preventing future SRs; most people are stung infrequently, most SRs resolve without long-term consequences, and a fatal outcome is extremely rare. VIT only becomes cost effective if one is stung frequently (eg, beekeepers or if quality of life improvement is considered. Thus, for most people with insect sting allergy, anxiety and quality of life impairment should be the overriding consideration when making treatment decisions, highlighting the importance of a patient-centered approach. Areas which need to be explored in future research include efforts to improve the safety and convenience of VIT such as the use of sublingual immunotherapy; quality of life effects of venom allergy in children and adolescents as well as their parents; and the optimal duration of treatment.Keywords: anaphylaxis, quality of life

  8. Targeting the immunoregulatory indoleamine 2,3 dioxygenase pathway in immunotherapy

    Science.gov (United States)

    Johnson, Burles A; Baban, Babak; Mellor, Andrew L

    2009-01-01

    Natural immune tolerance is a formidable barrier to successful immunotherapy to treat established cancers and chronic infections. Conversely, creating robust immune tolerance via immunotherapy is the major goal in treating autoimmune and allergic diseases, and enhancing survival of transplanted organs and tissues. In this review, we focus on a natural mechanism that creates local T-cell tolerance in many clinically relevant settings of chronic inflammation involving expression of the cytosolic enzyme indoleamine 2,3-dioxygenase (IDO) by specialized subsets of dendritic cells. IDO-expressing dendritic cells suppress antigen-specific T-cell responses directly, and induce bystander suppression by activating regulatory T cells. Thus, manipulating IDO is a promising strategy to treat a range of chronic inflammatory diseases. PMID:20161103

  9. Emerging Therapies for Stage III Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Sameera S. Kumar

    2017-09-01

    Full Text Available The current standard of care for locally advanced non-small cell lung cancer (NSCLC includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT has shown a high degree of safety and local control for stage I lung cancers and other localized malignancies. More recently, phase I/II studies using SBRT for dose escalation after conventional chemoradiation in locally advanced NSCLC have been promising with good apparent safety. Immunotherapy also offers opportunities to address distant disease and preclinical data suggest immunotherapy in tandem with SBRT may be a rational way to induce an “abscopal effect” although there are little clinical data as yet. By building on the proven concept of conventional chemoradiation for patients with locally advanced NSCLC with a subsequent radiation dose intensification to residual disease with SBRT concurrent with immunotherapy, we hope address the issues of metastatic and local failures. This “quadmodality” approach is still in its infancy but appears to be a safe and rational approach to the improving the outcome of NSCLC therapy.

  10. Awareness and understanding of cancer immunotherapy in Europe

    NARCIS (Netherlands)

    Mellstedt, H.; Gaudernack, G.; Gerritsen, W.R.; Huber, C.; Melero, I.; Parmiani, G.; Scholl, S.; Thatcher, N.; Wagstaff, J.; Zielinski, C.

    2014-01-01

    The use of immunotherapy in the management of cancer is growing, and a range of new immunotherapeutic strategies is becoming available. It is important that people involved in the care of cancer understand how cancer immunotherapies differ from conventional chemotherapy and apply this knowledge to

  11. Issues in stinging insect allergy immunotherapy: a review.

    Science.gov (United States)

    Finegold, Ira

    2008-08-01

    The treatment of insect allergy by desensitization still continues to present with some unanswered questions. This review will focus mainly on articles that have dealt with these issues in the past 2 years. With the publication in 2007 of Allergen Immunotherapy: a practice parameter second update, many of the key issues were reviewed and summarized. Other recent studies deal with omalizumab pretreatment of patients with systemic mastocytosis and very severe allergic reactions to immunotherapy. It would appear that venom immunotherapy is somewhat unique compared to inhalant allergen immunotherapy in that premedication prior to rush protocols may not be necessary and that intervals of therapy may be longer than with allergen immunotherapy. The use of concomitant medications such as beta-blockers may be indicated in special situations. Angiotensin-converting enzyme inhibitors can be stopped temporarily before venom injections to prevent reactions. The issue of when to discontinue immunotherapy remains unsettled and should be individualized to patient requirements. The newest revision of the Immunotherapy Parameters provides much needed information concerning successful treatment with immunotherapy of Hymenoptera-sensitive patients.

  12. Clinical experience of integrative cancer immunotherapy with GcMAF.

    Science.gov (United States)

    Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Mette, Martin; Uto, Yoshihiro; Hori, Hitoshi; Sakamoto, Norihiro

    2013-07-01

    Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum. The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily. By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective. The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>

  13. Specific allergen immunotherapy for the treatment of atopic eczema.

    Science.gov (United States)

    Tam, Herman; Calderon, Moises A; Manikam, Logan; Nankervis, Helen; García Núñez, Ignacio; Williams, Hywel C; Durham, Stephen; Boyle, Robert J

    2016-02-12

    also unable to determine whether sublingual immunotherapy was associated with more local adverse reactions compared with subcutaneous immunotherapy. Overall, the quality of the evidence was low. The low quality was mainly due to the differing results between studies, lack of blinding in some studies, and relatively few studies reporting participant-centred outcome measures. We found limited evidence that SIT may be an effective treatment for people with AE. The treatments used in these trials were not associated with an increased risk of local or systemic reactions. Future studies should use high quality allergen formulations with a proven track record in other allergic conditions and should include participant-reported outcome measures.

  14. The current status of immunotherapy in peritoneal carcinomatosis.

    Science.gov (United States)

    Ströhlein, Michael Alfred; Heiss, Markus Maria; Jauch, Karl-Walter

    2016-10-01

    Peritoneal carcinomatosis (PC) is a cancer disease with an urgent need for effective treatment. Conventional chemotherapy failed to show acceptable results. Cytoreductive surgery and hyperthermic chemoperfusion (HIPEC) are only beneficial in few patients with resectable peritoneal metastasis. Immunotherapy could be attractive against PC, as all requirements for immunotherapy are available in the peritoneal cavity. This review analyzes the present literature for immunotherapy of PC. Advances from immune stimulators, radionucleotide-conjugated- and bispecific antibodies to future developments like adoptive engineered T-cells with chimeric receptors are discussed. The clinical development of catumaxomab, which was the first intraperitoneal immunotherapy to be approved for clinical treatment, is discussed. The requirements for future developments are illustrated. Expert commentary: Immunotherapy of peritoneal carcinomatosis is manageable, showing striking cancer cell killing. Improved profiles of adverse events by therapy-induced cytokine release, enhanced specific killing and optimal treatment schedules within multimodal treatment will be key factors.

  15. Natural Killer T Cells in Cancer Immunotherapy

    Science.gov (United States)

    Nair, Shiny; Dhodapkar, Madhav V.

    2017-01-01

    Natural killer T (NKT) cells are specialized CD1d-restricted T cells that recognize lipid antigens. Following stimulation, NKT cells lead to downstream activation of both innate and adaptive immune cells in the tumor microenvironment. This has impelled the development of NKT cell-targeted immunotherapies for treating cancer. In this review, we provide a brief overview of the stimulatory and regulatory functions of NKT cells in tumor immunity as well as highlight preclinical and clinical studies based on NKT cells. Finally, we discuss future perspectives to better harness the potential of NKT cells for cancer therapy. PMID:29018445

  16. Ordinary Differential Equation Models for Adoptive Immunotherapy.

    Science.gov (United States)

    Talkington, Anne; Dantoin, Claudia; Durrett, Rick

    2018-05-01

    Modified T cells that have been engineered to recognize the CD19 surface marker have recently been shown to be very successful at treating acute lymphocytic leukemias. Here, we explore four previous approaches that have used ordinary differential equations to model this type of therapy, compare their properties, and modify the models to address their deficiencies. Although the four models treat the workings of the immune system in slightly different ways, they all predict that adoptive immunotherapy can be successful to move a patient from the large tumor fixed point to an equilibrium with little or no tumor.

  17. Immunotherapy with GD2 specific monoclonal antibodies

    International Nuclear Information System (INIS)

    Cheung, N.K.V.; Medof, E.M.; Munn, D.

    1988-01-01

    Targeted immunotherapy focuses anti-tumor activity of antibodies and effector cells, which are actively developed by the host or adoptively transferred, onto tumor cells and into tumor sites. Such tumor selective therapy can be more specific and efficient. The value of such an approach is evident in the classical interaction of antibodies. This paper reports that the ganglioside G D2 is an ideal antigen for specific tumor targeting because of its relative lack of heterogeneity among human neuroblastoma, its high density on tumor cells, its lack of antigen modulation upon binding to antibody, and its restricted distribution in normal tissues

  18. Allergen immunotherapy for insect venom allergy

    DEFF Research Database (Denmark)

    Dhami, S; Zaman, H; Varga, E-M

    2016-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety...... of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were...

  19. Influence of preseasonal treatment with L-tyrosine-adsorbed allergoids on IgE-mediated histamine release from basophils of children suffering from allergic diseases.

    Science.gov (United States)

    Wegner, F; Fenkes, A; Stemmann, E A; Reinhardt, D

    1981-04-01

    In 10 children suffering from allergic pollinosis and/or asthma, a preseasonal hyposensitization scheme with 3 weekly injections of a glutaraldehyde-modified, tyrosine-adsorbed grass-pollen allergen reduced the histamine release from basophils in response to increasing concentrations of antigen. The decrease in histamine release which occurred 1 week after the injection course was even maintained during the pollen season. The inhibition was only obtained when basophils were incubated with the serum of patients, but not with the serum of normals, indicating that blocking antibodies may have occurred. In contrast to what has been observed in the treated patients' group, 5 patients, who were not included in the hyposensitization scheme, showed identical histamine release curves during the whole investigation period. Specific IgE did not increase after the treatment course and shows the same behaviour as the untreated patients. Thus, as treatment with glutaraldehyde modified, tyrosine-adsorbed allergoids is safe to administer, requires only 3 injections, reduces histamine release from basophils by production of "blocking" antibodies, it appears to be a useful tool in the hyposensitization treatment.

  20. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Khinchi, M S; Poulsen, Lars K.; Carat, F

    2004-01-01

    Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed.......Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed....

  1. Angiosarcoma of the scalp treated with curative radiotherapy plus recombinant interleukin-2 immunotherapy

    International Nuclear Information System (INIS)

    Ohguri, Takayuki; Imada, Hajime; Nomoto, Satoshi; Yahara, Katsuya; Hisaoka, Masanori; Hashimoto, Hiroshi; Tokura, Yoshiki; Nakamura, Katsumasa; Shioyama, Yoshiyuki; Honda, Hiroshi; Terashima, Hiromi; Moroi, Yoiichi; Furue, Masutaka; Korogi, Yukunori

    2005-01-01

    Purpose: To evaluate the effectiveness of curative radiotherapy (RT) plus recombinant interleukin-2 (rIL-2) immunotherapy regarding the treatment results for angiosarcoma of the scalp. Curative resection of angiosarcoma of the scalp is usually difficult because of the diffuse, clinically undetectable local spread. RT is a rational therapeutic approach, because a wide region of the dermis can be treated, while sparing the underlying normal tissues. Recently, the effectiveness of immunotherapy with rIL-2 has also been reported in the treatment of angiosarcoma of the scalp. Methods and Materials: The data of 20 patients with angiosarcoma of the scalp treated with curative RT plus rIL-2 immunotherapy between January 1988 and June 2002 were retrospectively analyzed. The total radiation dose was 70.3 ± 6.9 Gy. The fractions were 2-3 Gy daily, given 5 d/wk. rIL-2 immunotherapy was performed by transcatheter arterial administration in 10 patients, systemic administration in 11 during the course of RT, and intratumoral injection in 10 during and/or after RT; 12 patients received a combination of two. Five patients underwent limited surgery, and concomitant pacilitaxel chemotherapy was also used in 2 patients. Results: The median survival time for overall, local recurrence-free, and distant metastasis-free survival was 36.2, 11.1, and 17.8 months, respectively. Local recurrence developed in 7 patients (35%), 4 of whom also had evidence of distant metastases. An additional 7 patients (35%) developed distant metastases alone. Recurrence within the radiation field was recognized in 2 patients with systemic rIL-2 administration alone (p < 0.05). Arterial or intratumoral administration combined with systemic administration of rIL-2 resulted in better distant metaststasis-free survival rates (p < 0.05). Conclusion: Curative RT plus rIL-2 immunotherapy provided an efficient, effective means of treating angiosarcoma of the scalp. Arterial or intratumoral administration combined

  2. Immunotherapy and immunoescape in colorectal cancer

    Science.gov (United States)

    Mazzolini, Guillermo; Murillo, Oihana; Atorrasagasti, Catalina; Dubrot, Juan; Tirapu, Iñigo; Rizzo, Miguel; Arina, Ainhoa; Alfaro, Carlos; Azpilicueta, Arantza; Berasain, Carmen; Perez-Gracia, José L; Gonzalez, Alvaro; Melero, Ignacio

    2007-01-01

    Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma. PMID:17990348

  3. Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

    Science.gov (United States)

    Coveler, Andrew L; Rossi, Gabriela R; Vahanian, Nicholas N; Link, Charles; Chiorean, E Gabriela

    2016-02-01

    Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

  4. Modeling Human Leukemia Immunotherapy in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Jinxing Xia

    2016-08-01

    Full Text Available The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL, which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI, a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.

  5. Advances in Cancer Immunotherapy in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Smitha Menon

    2016-11-01

    Full Text Available Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field.

  6. Cancer immunotherapy drives implementation science in oncology.

    Science.gov (United States)

    Speiser, Daniel E; Flatz, Lukas

    2014-01-01

    Cancer immunotherapy has come a long way. The hope that immunological approaches may help cancer patients has sparked many initiatives in research and development (R&D). For many years, progress was modest and disappointments were frequent. Today, the increasing scientific and medical knowledge has established a solid basis for improvements. Considerable clinical success was first achieved for patients with hematological cancers. More recently, immunotherapy has entered center stage in the development of novel therapies against solid cancers. Together with R&D in angiogenesis, the field of immunology has fundamentally extended the scientific scope, which has evolved from a cancer-cell-centered view to a comprehensive and integrated vision of tumor biology. Current R&D is focused on a large array of possible disease mechanisms, driven by cancer cells, and amplified by tumor stroma, inflammatory and immunological actors, blood and lymph vessels, and the “macroenvironment," i.e. systemic mechanisms of the host, particularly of the haematopoietic system. Contrasting to this large spectrum of pathophysiological events promoting tumor growth, only a small number of biological mechanisms, namely of the immune system, have the potential to counteract tumor growth. They are of prime interest because therapeutic enhancement may result in clinical benefit for patients. This special issue is dedicated to immunotherapeutics against cancer, with particular emphasis on vaccination and combination therapies, providing updates and extended insight in this booming field.

  7. Experimental study on an active specific immunotherapy modified with irradiation, 1

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Takashima, Hitoshi; Imanaka, Kazufumi

    1982-01-01

    Active specific immunotherapy using low-dose-irradiated tumor cells and activated mononuclear cells was studied on the transplanted MM 46 tumor of female C3H/He mice aged 12 weeks, after radiotherapy was performed. Local irradiation with the dose of 3,000 rads by high energy electron beam was performed on the fifth day after 5 x 10 6 tumor cells were inoculated in the right hind paws. Tumor cells and mononuclear cells were separated from the tumor tissue which was irradiated with the dose of 2,000 rads on the fifth day and were injected subcutaneously into the left hind paws of the tumor burden mice on the eleventh day. Anti-tumor effect was evaluated by the changes of the tumor volume and survival curves. Tumor growth was significantly inhibited in the group which received irradiation combined with active specific immunotherapy compared with the control group (p < 0.01). Survival rate was significantly higher in the group which received irradiation combined with active specific immunotherapy than the control group (p < 0.025). (author)

  8. Immunological comparison of allergen immunotherapy tablet treatment and subcutaneous immunotherapy against grass allergy

    DEFF Research Database (Denmark)

    Aasbjerg, K; Backer, V; Lund, G

    2014-01-01

    BACKGROUND: IgE-mediated allergic rhinitis to grass pollen can successfully be treated with either allergen immunotherapy tablets (SLIT tablet) or SQ-standardized subcutaneous immunotherapy (SCIT). The efficacy of these two treatment modalities for grass allergy is comparable, but the immunological...... mechanisms may differ. ClinicalTrials.gov ID: NCT01889875. OBJECTIVES: To compare the immunological changes induced by SQ-standardized SCIT and SLIT tablet. METHODS: We randomized 40 individuals with grass pollen rhinitis into groups receiving SCIT, SLIT tablet, or neither and followed them for 15 months...... differed significantly in both SCIT and SLIT-tablet treatment groups when compared to the control group. Both SCIT and SLIT-tablet groups were significantly different from the control group after 1–3 months of treatment. In general, the changes induced by SCIT reached twice that of SLIT tablet...

  9. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 9

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji

    1983-01-01

    We have already reported the remarkable effect of an active specific immunotherapy using cryopreserved tumor cells and infiltrating mononuclear cells prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, OK-432 combined with the active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM 46 tumor cells were received local radiotherapy with a dose of 3,000 rads by high energy electron beams on the fifth day after inoculation. The tumor cells and infiltrating mononuclear cells cryopreserved for two months were thawed and treated with mitomycin-C at concentration of 20 μg/10 7 cells at 37 0 C for 30 min. Then, these cells were injected subcutaneously into the left hind paws as a mitomycin C-treated, cryopreserved active specific immunotherapy on the thirteenth day, and daily dose of 1 KE of OK-432 was injected intraperitoneally from the sixth to the tenth days. The inhibition of the tumor growth was similarly observed in the group which received this active specific immunotherapy combined with a biological response modifier, OK-432. (author)

  10. Allergen immunotherapy for the prevention of allergy

    DEFF Research Database (Denmark)

    Kristiansen, Maria; Dhami, Sangeeta; Netuveli, Gopal

    2017-01-01

    BACKGROUND: There is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease. METHODS: Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using...... was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30-0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence...... random-effects meta-analyses. RESULTS: A total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04-2.09) and no randomized controlled evidence...

  11. Nanoparticle based-immunotherapy against allergy.

    Science.gov (United States)

    Gamazo, Carlos; Gastaminza, Gabriel; Ferrer, Marta; Sanz, María L; Irache, Juan M

    2014-01-01

    Allergic diseases are one of the most prevalent diseases, reaching epidemic proportions in developed countries. An allergic reaction occurs after contact with an environmental protein, such as inhalants allergens (pollen, animal dander, house dust mites), or food proteins. This response is known as part of the type 2 immunity that is counterbalanced by Type 1 immunity and Tregs. Widely used allergen-specific immunotherapy (IT) is a long term treatment to induce such switch from Th2 to Th1 response. However, conventional IT requires multiple allergen injections over a long period of time and is not free of risk of producing allergic reactions. As a consequence, new safer and faster immunotherapeutic methods are required. This review deals with allergen IT using nanoparticles as allergen delivery system that will allow a different way of administration, reduce dose and diminish allergen exposure to IgE bound to mast cells or basophils.

  12. Modulation of GITR for cancer immunotherapy

    Science.gov (United States)

    Schaer, David A; Murphy, Judith T; Wolchok, Jedd D

    2012-01-01

    Modulation of co-inhibitory and co-stimulatory receptors of the immune system has become a promising new approach for immunotherapy of cancer. With the recent FDA approval of CTLA-4 blockade serving as an important proof of principal, many new targets are now being translated into the clinic. Preclinical research has demonstrated that targeting glucocorticoid-induced tumor necrosis factor (TNF) receptor related gene (GITR), a member of TNF receptor superfamily, by agonist antibodies or natural ligand, can serve as an effective anti-tumor therapy. In this review, we will cover this research and the rationale that has led to initiation of two phase 1 clinical trials targeting GITR as a new immunotherapeutic approach for cancer. PMID:22245556

  13. The Role of Immunotherapy in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Mehmet Kocoglu

    2016-01-01

    Full Text Available Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards better understanding of normal and missing immune surveillence in myeloma have led to development of new strategies and therapies that require the engagement of the immune system. Many of these treatments are under clinical development and have already started providing encouraging results. We, for the second time in the last two decades, are about to witness another shift of the paradigm in the management of this ailment. This review will summarize the major approaches in myeloma immunotherapies.

  14. Cancer immunotherapy: avoiding the road to perdition

    Directory of Open Access Journals (Sweden)

    Bright Robert K

    2004-07-01

    Full Text Available Abstract The hypothesis that human cancers express antigens that can be specifically targeted by cell mediated immunity has become a scientifically justifiable rationale for the design and clinical testing of novel tumor-associated antigens (TAA. Although a number of TAA have been recognized and it has been suggested that they could be useful in the immunological treatment of cancer, the complexity of human beings leads us to reflect on the need to establish new criteria for validating their real applicability. Herein, we show a system level-based approach that includes morphological and molecular techniques, which is specifically required to improve the capacity to produce desired results and to allow cancer immunotherapy to re-emerge from the mist in which it is currently shrouded.

  15. Intravenous immunoglobulin and Alzheimer's disease immunotherapy.

    Science.gov (United States)

    Solomon, Beka

    2007-02-01

    Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.

  16. Targetless T cells in cancer immunotherapy

    DEFF Research Database (Denmark)

    thor Straten, Eivind Per; Garrido, Federico

    2016-01-01

    Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell...... infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However......, it is also well established that cancer cells are often characterized by loss or down regulation of HLA class I molecules, documented in a variety of human tumors. Consequently, immune therapy building on CD8 T cells will be futile in patients harboring HLA class-I negative or deficient cancer cells...

  17. New visions in specific immunotherapy in children

    DEFF Research Database (Denmark)

    Halken, Susanne; Lau, Susanne; Valovirta, Erkka

    2008-01-01

    of the effect, as well as the dose, the treatment regimen and duration has not been sufficiently elaborated. It is demonstrated that SCIT has the potential for preventing the development of asthma in children with allergic rhinoconjunctivitis. Also one randomized study indicates a preventive effect of SLIT...... in children on the development of asthma. At present, there are no studies who clearly demonstrates either a long-term effect or a preventive effect on the development of asthma of SLIT in children. The areas with lack of evidence should be addressed in well performed prospective, randomized long-term studies...... immunotherapy (SLIT) has also been investigated in children. SCIT, especially with grass and birch pollens but also house dust mites, is an effective treatment in children with allergic rhinitis and asthma when a significant part of their symptoms are caused by these allergens. A long-term effect up to 12 yr...

  18. Cancer immunotherapy: potential involvement of mediators

    Directory of Open Access Journals (Sweden)

    S. Ben-Efraim

    1997-01-01

    Full Text Available The description of a cell-free soluble anti-tumour factor by Carswell et al. in 1975 (Proc Natl Acad Sci USA, 72: 3666–3670 was followed by a long series of experimental and clinical investigations into the role of cell-free mediators in cancer immunotherapy. These investigations included research on the effects of macrophage–derived eicosanoids (cycloxygenase and lipoxygenase derivates of arachidonic acid and of monokines such as tumour necrosis factor-α, interleukin-1 and granulocyte–monocyte–macrophage–colony stimulating factor and of lymphocyte products: interleukins and interferons. The investigations yielded information on the effects of various factors on macrophage and T-cell activation in vitro, determination of direct anti-tumour properties on animal and human tumour cells in vitro and on therapeutic effectiveness in tumour-bearing individuals either alone or in combination with other therapeutic factors and their production by tumour cells. During recent years much effort has been dedicated towards the use of the tumour cells transfected with cytokine genes in the preparation of cancer vaccines. Cycloxygenase products (prostaglandins were usually assumed to inhibit expression of anti-tumour activity by macrophages and an increase in their production in cancer patients was considered as a poor prognostic index. Lipoxygenase (leukotrienes products were assumed to exhibit antitumour activity and to induce production of IL-1 by macrophages. Interleukins 2, 4, 6, 7, 12 and the interferons were extensively tested for their therapeutic effectiveness in experimental tumour models and in cancer clinical trials. The general conclusion on the use of cell-free mediators for cancer immunotherapy is that much still has to be done in order to assure effective and reproducible therapeutic effectiveness for routine use in the treatment of human neoplasia.

  19. Nanoparticle–allergen complexes for allergen immunotherapy

    Directory of Open Access Journals (Sweden)

    Di Felice G

    2017-06-01

    Full Text Available Gabriella Di Felice,1 Paolo Colombo2 1National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, 2Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy Abstract: Allergen-specific immunotherapy was introduced in clinical settings more than 100 years ago. It remains the only curative approach to treating allergic disorders that ameliorates symptoms, reduces medication costs, and blocks the onset of new sensitizations. Despite this clinical evidence and knowledge of some immunological mechanisms, there remain some open questions regarding the safety and efficacy of this treatment. This suggests the need for novel therapeutic approaches that attempt to reduce the dose and frequency of treatment administration, improving patient compliance, and reducing costs. In this context, the use of novel adjuvants has been proposed and, in recent years, biomedical applications using nanoparticles have been exploited in the attempt to find formulations with improved stability, bioavailability, favorable biodistribution profiles, and the capability of targeting specific cell populations. In this article, we review some of the most relevant regulatory aspects and challenges concerning nanoparticle-based formulations with immunomodulatory potential, their related immunosafety issues, and the nature of the nanoparticles most widely employed in the allergy field. Furthermore, we report in vitro and in vivo data published using allergen/nanoparticle systems, discuss their impact on the immune system in terms of immunomodulatory activity and the reduction of side effects, and show that this strategy is a novel and promising tool for the development of allergy vaccines. Keywords: allergy, nanocarriers, immunotoxicity, immune modulation, immunotherapy, allergens

  20. Immunotherapy in Melanoma, Gastrointestinal (GI, and Pulmonary Malignancies

    Directory of Open Access Journals (Sweden)

    Alexander B. Dillon

    2015-03-01

    Full Text Available Oncologic immunotherapy involves stimulating the immune system to more effectively identify and eradicate tumor cells that have successfully adapted to survive the body's natural immune defenses. Immunotherapy has shown great promise thus far by prolonging the lives of patients with a variety of malignancies, and has added a crucial new set of tools to the oncologists' armamentarium. The aim of this paper is to provide an overview of immunotherapy treatment options that are currently available and under active research for melanoma, gastrointestinal (esophageal, gastric, pancreatic, and colorectal, and pulmonary malignancies. Potential biomarkers that may predict favorable responses to immunotherapies are discussed where applicable, as are future avenues of research in this rapidly evolving field.

  1. Immunotherapy in advanced melanoma: a network meta-analysis.

    Science.gov (United States)

    Pyo, Jung-Soo; Kang, Guhyun

    2017-05-01

    The aim of this study was to compare the effects of various immunotherapeutic agents and chemotherapy for unresected or metastatic melanomas. We performed a network meta-analysis using a Bayesian statistical model to compare objective response rate (ORR) of various immunotherapies from 12 randomized controlled studies. The estimated ORRs of immunotherapy and chemotherapy were 0.224 and 0.108, respectively. The ORRs of immunotherapy in untreated and pretreated patients were 0.279 and 0.176, respectively. In network meta-analysis, the odds ratios for ORR of nivolumab (1 mg/kg)/ipilmumab (3 mg/kg), pembrolizumab 10 mg/kg and nivolumab 3 mg/kg were 8.54, 5.39 and 4.35, respectively, compared with chemotherapy alone. Our data showed that various immunotherapies had higher ORRs rather than chemotherapy alone.

  2. Immunotherapy targets metastatic breast cancer–cell mutations

    Science.gov (United States)

    A novel approach to immunotherapy developed by NCI researchers led to the complete regression of breast cancer in a patient who was unresponsive to all other treatments. The findings were published in Nature Medicine.

  3. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, Andrea [Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057 (Switzerland); Wehner, Rebekka [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Füssel, Susanne [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Bachmann, Michael [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Wirth, Manfred P. [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Schmitz, Marc, E-mail: marc.schmitz@tu-dresden.de [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany)

    2012-02-22

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8{sup +} cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4{sup +} T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  4. Novel Approaches to Locoregional and Systemic Immunotherapy for Ovarian Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0298 TITLE: Novel approaches to locoregional and systemic immunotherapy for ovarian cancer PRINCIPAL INVESTIGATOR...Dmitriy Zamarin CONTRACTING ORGANIZATION: Memorial Sloan Kettering Cancer Center New York, NY 10017 REPORT DATE: October 2017 TYPE OF REPORT...TITLE AND SUBTITLE Novel approaches to locoregional and systemic immunotherapy for ovarian cancer 5a. CONTRACT NUMBER vel ap roaches to l c regional

  5. Adjuvant immunotherapy after surgery and radiotherapy for breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Papavasiliou, C.; Pappas, J.; Pavlatou, M.; Keramopoulos, A.; Giannakoulis, N.; Koumantakis, E.; Nicolaidis, C.

    1982-04-01

    One hundred patients with operable breast cancer received 'prophylactic' postoperative irradiation after mastectomy. In addition, during irradiation and for four months afterwards, part of the patients received immunotherapy (BCG scarification and oral administration of levamisole), while the rest served as controls. Although survival time in the two groups was about the same, disease-free survival time was significantly longer in the immunotherapy group. Tumor reactivation was preceded by deterioration of the Leucocyte Migration Inhibition Index.

  6. Adjuvant immunotherapy after surgery and radiotherapy for breast carcinoma

    International Nuclear Information System (INIS)

    Papavasiliou, C.; Pappas, J.; Pavlatou, M.; Keramopoulos, A.; Giannakoulis, N.; Koumantakis, E.; Nicolaidis, C.

    1982-01-01

    One hundred patients with operable breast cancer received 'prophylactic' postoperative irradiation after mastectomy. In addition, during irradiation and for four months afterwards, part of the patients received immunotherapy (BCG scarification and oral administration of levamisole), while the rest served as controls. Although survival time in the two groups was about the same, disease-free survival time was significantly longer in the immunotherapy group. Tumor reactivation was preceded by deterioration of the Leucocyte Migration Inhibition Index. (orig.) [de

  7. The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Delia Nelson

    2014-01-01

    Full Text Available Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more “full frontal” treatments such as transfer of large numbers of laboratory-expanded tumor-specific cytotoxic T lymphocytes or large intravenous doses of cytokine. Numerous studies have demonstrated that intratumoural therapy has the capacity to minimizing local suppression, inducing sufficient “dangerous” tumor cell death to cross-prime strong immune responses, and rending tumor blood vessels amenable to immune cell traffic to induce effector cell changes in secondary lymphoid organs. However, the key to its success is the design of a sound rational approach based on evidence. There is compelling preclinical data for local immunotherapy approaches in tumor immunology. This review summarises how immune events within a tumour can be modified by local approaches, how this can affect systemic antitumor immunity such that distal sites are attacked, and what approaches have been proven most successful so far in animals and patients.

  8. Impact of immunotherapy among patients with melanoma brain metastases managed with radiotherapy.

    Science.gov (United States)

    Stokes, William A; Binder, David C; Jones, Bernard L; Oweida, Ayman J; Liu, Arthur K; Rusthoven, Chad G; Karam, Sana D

    2017-12-15

    Patients with melanoma brain metastases (MBM) have been excluded from trials evaluating immunotherapy in melanoma. As such, immunotherapy's role in MBM is poorly understood, particularly in combination with radiotherapy. The National Cancer Database was queried for patients with MBM receiving brain radiotherapy. They were classified according to immunotherapy receipt. Multivariate Cox regression was performed to identify factors associated with survival. Among 1287 patients, 185 received immunotherapy. Factors associated with improved survival included younger age, academic facility, lower extracranial disease burden, stereotactic radiotherapy, chemotherapy, and immunotherapy. Adding immunotherapy to radiotherapy for MBM is associated with improved survival. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Sublingual immunotherapy: World Allergy Organization position paper 2013 update

    Science.gov (United States)

    2014-01-01

    We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations. Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. PMID:24679069

  10. Temperature control in interstitial laser cancer immunotherapy

    Science.gov (United States)

    Bandyopadhyay, Pradip K.; Holmes, Kyland; Burnett, Corinthius; Zharov, Vladimir P.

    2003-07-01

    Positive results of Laser-Assisted Cancer Immunotherapy (LACI) have been reported previously in the irradiation of superficial tumors. This paper reports the effect of LACI using laser interstitial therapy approach. We hypothesize that the maximum immuno response depends on laser induced tumor temperature. The measurement of tumor temperature is crucial to ensure necrosis by thermal damage and immuno response. Wister Furth female rats in this study were inoculated with 13762 MAT B III rat mammary adinocarcinoma. LACI started seven to ten days following inoculation. Contrary to surface irradation, we applied laser interstitial irradiation of tumor volume to maximize the energy deposition. A diode laser with a wavelength of 805 nm was used for tumor irradiation. The laser energy was delivered inside the tumor through a quartz fiber. Tumor temperature was measured with a micro thermocouple (interstitial), while the tumor surface temperature was controlled with an IR detector. The temperature feedback demonstrates that it is possible to maintain the average tumor temperature at the same level with reasonable accuracy in the desired range from 65°C-85°C. In some experiments we used microwave thermometry to control average temperature in deep tissue for considerable period of time, to cause maximum thermal damage to the tumor. The experimental set-up and the different temperature measurement techniques are reported in detail, including the advantages and disadvantages for each method.

  11. MHC class II molecules and tumour immunotherapy

    International Nuclear Information System (INIS)

    Oven, I.

    2005-01-01

    Background. Tumour immunotherapy attempts to use the specificity and capability of the immune system to kill malignant cells with a minimum damage to normal tissue. Increasing knowledge of the identity of tumour antigens should help us design more effective therapeutic vaccines. Increasing evidence has demonstrated that MHC class II molecules and CD4+ T cells play important roles in generating and maintaining antitumour immune responses in animal models. These data suggest that it may be necessary to involve both CD4+ and CD8+ T cells for more effective antitumour therapy. Novel strategies have been developed for enhancing T cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells, by the inclusion of MHC class II-restricted tumour antigens and by genetically modifying tumour cells to present antigen to T lymphocytes directly. Conclusions. Vaccines against cancers aim to induce tumour-specific effector T cells that can reduce tumour mass and induce development of tumour-specific T cell memory, that can control tumour relapse. (author)

  12. Sarcoma Immunotherapy: Past Approaches and Future Directions

    Science.gov (United States)

    D'Angelo, S. P.; Tap, W. D.; Schwartz, G. K.; Carvajal, R. D.

    2014-01-01

    Sarcomas are heterogeneous malignant tumors of mesenchymal origin characterized by more than 100 distinct subtypes. Unfortunately, 25–50% of patients treated with initial curative intent will develop metastatic disease. In the metastatic setting, chemotherapy rarely leads to complete and durable responses; therefore, there is a dire need for more effective therapies. Exploring immunotherapeutic strategies may be warranted. In the past, agents that stimulate the immune system such as interferon and interleukin-2 have been explored and there has been evidence of some clinical activity in selected patients. In addition, many cancer vaccines have been explored with suggestion of benefit in some patients. Building on the advancements made in other solid tumors as well as a better understanding of cancer immunology provides hope for the development of new and exciting therapies in the treatment of sarcoma. There remains promise with immunologic checkpoint blockade antibodies. Further, building on the success of autologous cell transfer in hematologic malignancies, designing chimeric antigen receptors that target antigens that are over-expressed in sarcoma provides a great deal of optimism. Exploring these avenues has the potential to make immunotherapy a real therapeutic option in this orphan disease. PMID:24778572

  13. Oncolytic viruses: a step into cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Pol JG

    2011-12-01

    Full Text Available Jonathan G Pol, Julien Rességuier, Brian D LichtyMcMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, CanadaAbstract: Oncolytic virotherapy is currently under investigation in phase I–III clinical trials for approval as a new cancer treatment. Oncolytic viruses (OVs selectively infect, replicate in, and kill tumor cells. For a long time, the therapeutic efficacy was thought to depend on the direct viral oncolysis (virocentric view. The host immune system was considered as a brake that impaired virus delivery and spread. Attention was paid primarily to approaches enhancing virus tumor selectivity and cytotoxicity and/or that limited antiviral responses. Thinking has changed over the past few years with the discovery that OV therapy was also inducing indirect oncolysis mechanisms. Among them, induction of an antitumor immunity following OV injection appeared to be a key factor for an efficient therapeutic activity (immunocentric view. Indeed, tumor-specific immune cells persist post-therapy and can search and destroy any tumor cells that escape the OVs, and thus immune memory may prevent relapse of the disease. Various strategies, which are summarized in this manuscript, have been developed to enhance the efficacy of OV therapy with a focus on its immunotherapeutic aspects. These include genetic engineering and combination with existing cancer treatments. Several are currently being evaluated in human patients and already display promising efficacy.Keywords: oncolytic virus, cancer immunotherapy, tumor antigen, cancer vaccine, combination strategies

  14. Mechanisms of allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Fujita Hiroyuki

    2012-01-01

    Full Text Available Abstract Allergen-specific immunotherapy (allergen-SIT is a potentially curative treatment approach in allergic diseases. It has been used for almost 100 years as a desensitizing therapy. The induction of peripheral T cell tolerance and promotion of the formation of regulatory T-cells are key mechanisms in allergen-SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg cells and inducible IL-10- and TGF-β-producing type 1 Treg (Tr1 cells may prevent the development of allergic diseases and play a role in successful allergen-SIT and healthy immune response via several mechanisms. The mechanisms of suppression of different pro-inflammatory cells, such as eosinophils, mast cells and basophils and the development of allergen tolerance also directly or indirectly involves Treg cells. Furthermore, the formation of non-inflammatory antibodies particularly IgG4 is induced by IL-10. Knowledge of these molecular basis is crucial in the understanding the regulation of immune responses and their possible therapeutic targets in allergic diseases.

  15. Allergen extracts for immunotherapy in Latin America

    Directory of Open Access Journals (Sweden)

    Ricardo Cardona-Villa

    2018-04-01

    Full Text Available Background: The Latin American Society of Allergy, Asthma, and Immunology (SLAAI presents a document about the use of immunotherapy (IT in Latin America, where administration patterns, indications and contraindications, effects on health, adverse events and socioeconomic impact are reviewed. Objective: To review publications analyzing the use of IT in Latin America. Methods: A literature review was carried out in order to identify works addressing IT in Latin America. This review was focused on practical scientific information available on IT in the region, and a parallel comparison was made with practices observed in the United States and European countries. Results: Of the 21 Latin American countries included, only 9 had original articles meeting the selection criteria; a total of 82 articles were selected, most of them from Brazil and Mexico. Most widely used allergenic extracts in Latin America tropical and subtropical regions were those of mites and pollen. Conclusion: Although it is true that there are huge challenges for the future of IT in Latin America, studies on subcutaneous IT and sublingual IT are increasing, but most of them are retrospective and some have design bias, and more prospective studies are therefore required, using internationally validated scales for clinical evaluation.

  16. Role of Antigen Spread and Distinctive Characteristics of Immunotherapy in Cancer Treatment

    NARCIS (Netherlands)

    Gulley, J.L.; Madan, R.A.; Pachynski, R.; Mulders, P.; Sheikh, N.A.; Trager, J.; Drake, C.G.

    2017-01-01

    Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple

  17. FAST: Towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies

    NARCIS (Netherlands)

    Zuidmeer-Jongejan, Laurian; Fernandez-Rivas, Montserrat; Poulsen, Lars K.; Neubauer, Angela; Asturias, Juan; Blom, Lars; Boye, Joyce; Bindslev-Jensen, Carsten; Clausen, Michael; Ferrara, Rosa; Garosi, Paula; Huber, Hans; Jensen, Bettina M.; Koppelman, Stef; Kowalski, Marek L.; Lewandowska-Polak, Anna; Linhart, Birgit; Maillere, Bernard; Mari, Adriano; Martinez, Alberto; Mills, Clare En; Nicoletti, Claudio; Opstelten, Dirk-Jan; Papadopoulos, Nikos G.; Portoles, Antonio; Rigby, Neil; Scala, Enrico; Schnoor, Heidi J.; Sigursdottir, Sigurveig; Stavroulakis, Georg; Stolz, Frank; Swoboda, Ines; Valenta, Rudolf; van den Hout, Rob; Versteeg, Serge A.; Witten, Marianne; van Ree, Ronald

    2012-01-01

    ABSTRACT: The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT), using subcutaneous injections with

  18. TU-EF-210-01: HIFU, Drug Delivery, and Immunotherapy

    International Nuclear Information System (INIS)

    Ferrara, K.

    2015-01-01

    The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare

  19. TU-EF-210-01: HIFU, Drug Delivery, and Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferrara, K. [University of California - Davis (United States)

    2015-06-15

    The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

  20. Temperature distribution in target tumor tissue and photothermal tissue destruction during laser immunotherapy

    Science.gov (United States)

    Doughty, Austin; Hasanjee, Aamr; Pettitt, Alex; Silk, Kegan; Liu, Hong; Chen, Wei R.; Zhou, Feifan

    2016-03-01

    Laser Immunotherapy is a novel cancer treatment modality that has seen much success in treating many different types of cancer, both in animal studies and in clinical trials. The treatment consists of the synergistic interaction between photothermal laser irradiation and the local injection of an immunoadjuvant. As a result of the therapy, the host immune system launches a systemic antitumor response. The photothermal effect induced by the laser irradiation has multiple effects at different temperature elevations which are all required for optimal response. Therefore, determining the temperature distribution in the target tumor during the laser irradiation in laser immunotherapy is crucial to facilitate the treatment of cancers. To investigate the temperature distribution in the target tumor, female Wistar Furth rats were injected with metastatic mammary tumor cells and, upon sufficient tumor growth, underwent laser irradiation and were monitored using thermocouples connected to locally-inserted needle probes and infrared thermography. From the study, we determined that the maximum central tumor temperature was higher for tumors of less volume. Additionally, we determined that the temperature near the edge of the tumor as measured with a thermocouple had a strong correlation with the maximum temperature value in the infrared camera measurement.

  1. Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

    Science.gov (United States)

    Nurmatov, U; Dhami, S; Arasi, S; Pajno, G B; Fernandez-Rivas, M; Muraro, A; Roberts, G; Akdis, C; Alvaro-Lozano, M; Beyer, K; Bindslev-Jensen, C; Burks, W; du Toit, G; Ebisawa, M; Eigenmann, P; Knol, E; Makela, M; Nadeau, K C; O'Mahony, L; Papadopoulos, N; Poulsen, L K; Sackesen, C; Sampson, H; Santos, A F; van Ree, R; Timmermans, F; Sheikh, A

    2017-08-01

    The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the

  2. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue

    International Nuclear Information System (INIS)

    Imanaka, Kazufumi; Tanaka, Koji; Sasai, Keisuke

    1984-01-01

    We have already reported the effectiveness of active specific immunotherapy based on the immune reaction of low-dose irradiated tumor tissue. In the present study, three kinds of immunotherapeutic methods subdivided by used cells were performed in order to compare each effectiveness. C3H/He mice bearing MM 46 tumor transplanted in the right hind paws received local irradiation with the dose of 3,000 rad on the 6th day, and the above-mentioned three methods, using tumor cells, lymphocytes, and tumor cells combining lymphocytes which were all separated from the topical tumor tissue exposed to 2,000 rad, were applied respectively on the 14 th day. The most effective data were obtained from two groups treated by the immunotherapy with tumor cells combining lymphocytes, which virtually caused the longest survival and best tumor growth control. (author)

  3. Are ovarian cancer stem cells the target for innovative immunotherapy?

    Directory of Open Access Journals (Sweden)

    Wang L

    2018-05-01

    Full Text Available Liang Wang, Tianmin Xu, Manhua Cui Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China Abstract: Cancer stem cells (CSCs, a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment. Since CSCs are generally resistant to conventional therapies (chemotherapy and radiotherapy, immunotherapy is a more effective method that has been implemented in the clinic. Chimeric antigen receptor (CAR- T cell, an adoptive cellular immunotherapy, which results in apparent elimination of tumor in both hematologic and solid cancers, could be used for ovarian cancer. This review covers the basic conception of CSCs and OCSCs, the implication of epigenetic mechanism underlying cancer evolution considering CSC model, the immunotherapies reported for ovarian cancer targeting OCSCs currently, and the relationship between immune system and hierarchy cancer organized by CSCs. Particularly, the promising prospects and potential pitfalls of targeting OCSC surface markers to design CAR-T cellular immunotherapy are discussed here. Keywords: cancer stem cells, ovarian cancer, epigenetics, tumor cell surface marker, immunotherapy, CAR

  4. Safety considerations in providing allergen immunotherapy in the office.

    Science.gov (United States)

    Mattos, Jose L; Lee, Stella

    2016-06-01

    This review highlights the risks of allergy immunotherapy, methods to improve the quality and safety of allergy treatment, the current status of allergy quality metrics, and the future of quality measurement. In the current healthcare environment, the emphasis on outcomes measurement is increasing, and providers must be better equipped in the development, measurement, and reporting of safety and quality measures. Immunotherapy offers the only potential cure for allergic disease and asthma. Although well tolerated and effective, immunotherapy can be associated with serious consequence, including anaphylaxis and death. Many predisposing factors and errors that lead to serious systemic reactions are preventable, and the evaluation and implementation of quality measures are crucial to developing a safe immunotherapy practice. Although quality metrics for immunotherapy are in their infancy, they will become increasingly sophisticated, and providers will face increased pressure to deliver safe, high-quality, patient-centered, evidence-based, and efficient allergy care. The establishment of safety in the allergy office involves recognition of potential risk factors for anaphylaxis, the development and measurement of quality metrics, and changing systems-wide practices if needed. Quality improvement is a continuous process, and although national allergy-specific quality metrics do not yet exist, they are in development.

  5. ALLERGEN-SPECIFIC IMMUNOTHERAPY IN CHILDREN WITH POLLINOSIS

    Directory of Open Access Journals (Sweden)

    R. M. Torshkhoeva

    2014-01-01

    Full Text Available Aim: to compare clinical efficacy and safety of sublingual and parenteral allergen-specific immunotherapy in children with pollinosis. Patients and methods: 143 patients with pollinosis aged from 5 to 16 years old were included into the study. They were divided into 4 groups and received allergen-specific immunotherapy. Patients of the groups I and III were administered water-salt mixtures of extracts of tree pollen allergens. Patients from the II group received standardized adjuvant mixture of extracts of tree pollen allergens. Patients from the IV group were administered standardized extract of birch pollen allergens. Prophylaxis with water-salt solutions was performed before seasons of increased allergy risk during 3 years in autumns and winters. Prophylaxis with standardized extracts of allergens was performed uninterruptedly for 3 years. Results: allergen-specific immunotherapy prevents increase of sensitization and enlargement of allergen spectrum of elevated organism perceptibility, as well as prevents aggravation of disease course and conversion to more severe forms. It also decreases requirements of anti-allergic drugs and therefore elongates the duration of remission. Conclusions: allergen-specific immunotherapy with the use of standardized allergens is the most effective method of treatment of pollen sensitization in children. In order to increase its efficacy not less than 3 courses of immunotherapy are needed.

  6. Advances in Immunotherapy for Melanoma: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Carmen Rodríguez-Cerdeira

    2017-01-01

    Full Text Available Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

  7. Selection of patients for sublingual versus subcutaneous immunotherapy.

    Science.gov (United States)

    Larenas Linnemann, Désirée E S; Blaiss, Michael S

    2014-01-01

    Allergen immunotherapy is the sole treatment for IgE-mediated allergic diseases directed at the underlying mechanism. The two widely accepted administration routes are sublingual (SLIT) and subcutaneous (SCIT). We reviewed how patients should best be selected for immunotherapy and how the optimal administration route can be defined. Before deciding SCIT or SLIT, appropriate selection of patients for allergen immunotherapy (AIT) is mandatory. To be eligible for AIT, subjects must have a clear medical history of allergic disease, with exacerbation of symptoms on exposure to one or more allergens and a corresponding positive skin or in vitro test. Then the route of administration should be based on: published evidence of clinical and immunologic efficacy (which varies per allergic disease and per allergen); mono- or multi-allergen immunotherapy, for SLIT multi-allergen immunotherapy was not effective; safety: adverse events with SLIT are more frequent, but less severe; and, costs and patient preferences, closely related to adherence issues. All these are discussed in the article.

  8. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Brian J. [Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Pollack, Ian F. [Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Okada, Hideho, E-mail: okadah@upmc.edu [Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States)

    2013-11-01

    Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas.

  9. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    International Nuclear Information System (INIS)

    Ahn, Brian J.; Pollack, Ian F.; Okada, Hideho

    2013-01-01

    Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas

  10. A second chance for telomerase reverse transcriptase in anticancer immunotherapy.

    Science.gov (United States)

    Zanetti, Maurizio

    2017-02-01

    Telomerase reverse transcriptase (TERT) is a self-antigen that is expressed constitutively in many tumours, and is, therefore, an important target for anticancer immunotherapy. In the past 10 years, trials of immunotherapy with TERT-based vaccines have demonstrated only modest benefits. In this Perspectives, I discuss the possible immunological reasons for this limited antitumour efficacy, and propose that advances in our understanding of the genetics and biology of the involvement of TERT in cancer provides the basis for renewed interest in TERT- based immunotherapy. Telomerase and TERT are expressed in cancer cells at every stage of tumour evolution, from the cancer stem cell to circulating tumour cells and tumour metastases. Many cancer types also harbour cells with mutations in the TERT promoter region, which increase transcriptional activation of this gene. These new findings should spur new interest in the development of TERT-based immunotherapies that are redesigned in line with established immunological considerations and working principles, and are tailored to patients stratified on the basis of TERT-promoter mutations and other underlying tumour characteristics. Thus, despite the disappointment of previous clinical trials, TERT offers the potential for personalized immunotherapy, perhaps in combination with immune-checkpoint inhibition.

  11. Combination immunotherapy with prostate GVAX and ipilimumab: safety and toxicity.

    Science.gov (United States)

    Karan, Dev; Van Veldhuizen, Peter

    2012-06-01

    Evaluation of: van den Eertwegh AJ, Versluis J, van den Berg HP et al. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a Phase 1 dose-escalation trial. Lancet Oncol. 13(5), 509 – 517 (2012). A significant interest in the development of therapeutic cancer vaccines over the last decade has led to an improvement in overall survival of cancer patients in several clinical trials. As a result, two active immunotherapy agents, sipuleucel-T and ipilimumab, have been approved by the US FDA for the treatment of prostate cancer and melanoma, respectively. GVAX(®) cellular vaccine (Cell Genesysis, Inc., CA, USA) is another active immunotherapy agent targeting prostate cancer and it has been well studied in various clinical trials. The current publication, by van den Eertwegh et al., demonstrated a combination of two active immunotherapy approaches, using GVAX and ipilimumab for the treatment of metastatic castration-resistant prostate cancer. While GVAX is designed to amplify the antitumor response specific to prostate cancer cells, ipilimumab contributes to T-cell activation. Thus, the authors presented the possibility of augmenting antitumor T-cell activity in two different ways. They successfully demonstrated a tolerable dose and safety profile of ipilimumab in combination with GVAX for patients with metastatic castration-resistant prostate cancer. However, further studies of such immunotherapy combinations and detailed analysis of their immunological effects are needed to observe clinical benefit.

  12. Changes in Peak Flow Value during Immunotherapy Administration

    International Nuclear Information System (INIS)

    Saporta, D.

    2012-01-01

    Nasal allergies are prevalent affecting a large percentage of the population. Not only the upper respiratory tract but the whole body is involved. Allergies produce morbidity (and even occasional mortality) as they can lead to asthma development, and increased number of accidents. Immunotherapy results can be evaluated by following symptom scores, medication use, and objective measurements. Using a Peak Flow Meter (Pf) to evaluate immunotherapy results, it became evident that patients with and without asthma exhibited an improvement in the Peak Flow (PF) value, suggesting that lower airway involvement in allergic patients could be more prevalent than assumed. A consecutive chart review was performed including patients of any age with nasal allergies (with or without asthma) treated with immunotherapy for at least 6 months that had at least 2 complete evaluations. When immunotherapy was successful, most patients exhibited an increase in the PF value regardless of asthma status. A very significant finding was that most allergy sufferers may have lower airway inflammation. The use of the PF value to assess immunotherapy results and the potential failure to diagnose asthma in allergy sufferers are discussed. A better diagnosis of lower airway inflammation could be substantial in the management of these patients pulmonary function

  13. ADVERSE REACTIONS TO VACCINES AND WAYS OF ITS PREVENTION

    Directory of Open Access Journals (Sweden)

    Yelyseyeva I. V

    2011-04-01

    Full Text Available The overview concerns allergic reaction on vaccines and possible ways of increasing safety of immunization on basis of use of local specific immunotherapies (SIT experience, particularly the sublingual route. The use of chemically altered allergens, allergoids; alternative routes of administration, particularly the sublingual route; use of novel adjuvants, such as CpG oligonucleotides and mycobacterial vaccines; other approaches, such as allergenic peptides, relevant T-cell epitope peptide immunotherapy; DNA vaccination, recombinant and engineered allergens, chimeric molecules and combined therapy are all approaches that have yielded positive results to increase safety of SIT and improve its efficacy.

  14. Immunotherapy counteracting the immuno-depressive effect of radio and chemotherapy

    International Nuclear Information System (INIS)

    Robinson, E.; Bartal, A.; Cohen, Y.; Mekori, T.

    1977-01-01

    Surgery, radiotherapy and chemotherapy effect cures in a portion of cancer patients, but these treatments depress the immune system of the host. The purpose of our work was to find whether immunotherapy would abolish the depressive effect of the conventional treatment and thereby increase the percentage of cancer patients cured from their disease. The immunotherapeutic agent used was MER, a methanol extraction residue of the antituberculosis vaccine BCG. All patients had histologically proven neoplasia. The immunological responsiveness of the patients was evaluated before and after radiotherapy, chemotherapy and each MER treatment. The following immunological parameters were followed: (i) cutaneous delayed hypersensitivity to 3 recal antigens (PPD, SK-SD and Candidine); (ii) in vitro lymphocytic transformation to PHA and to the 3 above mentioned antigens. The patients were randomized into two groups. One group receiving injections of MER and the second acting as a control group. MER had no serious side effects and was well tolerated in most of the patients. The cutaneous reactivity became stronger and the lymphocytic stimulation index became higher after MER treatment. 51 patients with advanced lung cancer entered the trial. 29 were treated by MER after radiotherapy and/or chemotherapy and 22 control patients received only conventional therapy. There was no statistical significant difference in the survival between both groups, but it seems that in patients with locally advanced disease the survival was better in the MER group. MER treated group had less distant metastases which is in accord with the theory that immunotherapy is more effective in small tumours. Evidence points to the importance of the immune response in controlling the progression of malignant disease. Therefore, for neoplasia which cannot be controlled by surgery and/or radiotherapy and/or chemotherapy immunotherapy should be considered. (author)

  15. Rush immunotherapy for wasp venom allergy seems safe and effective in patients with mastocytosis.

    Science.gov (United States)

    Verburg, M; Oldhoff, J M; Klemans, R J B; Lahey-de Boer, A; de Bruin-Weller, M S; Röckmann, H; Sanders, C; Bruijnzeel-Koomen, C A F M; Pasmans, S G M A; Knulst, A C

    2015-11-01

    Patients with mastocytosis and wasp venom allergy (WA) may benefit from venom immunotherapy (VIT). However, fatal insect sting reactions have been described in mastocytosis patients despite previous immunotherapy. We investigated the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. To investigate the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. We describe nine patients with cutaneous mastocytosis and WA who received VIT. Cutaneous mastocytosis was confirmed by histopathology and systemic mastocytosis was diagnosed according to World Health Organization criteria. VIT was given according to a rush protocol. Given the difference in safety and efficacy of VIT in patients with WA and honeybee venom allergy, we reviewed the literature for VIT with the focus on WA patients with mastocytosis and addressed the difference between patients with cutaneous versus systemic mastocytosis. Nine patients had WA and mastocytosis, of whom six had cutaneous mastocytosis, two combined cutaneous and systemic mastocytosis and one systemic mastocytosis. All patients received rush IT with wasp venom. Most patients had only mild local side effects, with no systemic side effects during the course of VIT. One patient had a systemic reaction upon injection on one occasion, during the updosing phase, with dyspnoea and hypotension, but responded well to treatment. Immunotherapy was continued after temporary dose adjustment without problems. Two patients with a previous anaphylactic reaction were re-stung, without any systemic effects. VIT is safe in cutaneous mastocytosis patients with WA, while caution has to be made in case of systemic mastocytosis. VIT was effective in the patients who were re-stung.

  16. Immunotherapy for Urothelial Carcinoma: Current Status and Perspectives

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    Kitamura, Hiroshi, E-mail: hkitamu@sapmed.ac.jp; Tsukamoto, Taiji [Department of Urology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543 (Japan)

    2011-07-29

    Intravesical instillation of bacillus Calmette Guérin (BCG) for the treatment of urothelial carcinoma (UC) of the bladder is based on the BCG-induced immune response, which eradicates and prevents bladder cancer. The results of recent studies have suggested that not only major histocompatibility complex (MHC)-nonrestricted immune cells such as natural killer cells, macrophages, neutrophils, etc., but also MHC-restricted CD8{sup +} T cells play an important role and are one of the main effectors in this therapy. Better understanding of the mechanism of BCG immunotherapy supports the idea that active immunotherapy through its augmented T cell response can have great potential for the treatment of advanced UC. In this review, progress in immunotherapy for UC is discussed based on data from basic, translational and clinical studies. We also review the escape mechanism of cancer cells from the immune system, and down-regulation of MHC class I molecules.

  17. IMMUNOTHERAPY FOR EPSTEIN-BARR VIRUS-RELATED LYMPHOMAS

    Directory of Open Access Journals (Sweden)

    Alana Kennedy-Nasser

    2009-11-01

    Full Text Available Latent EBV infection is associated with several malignancies, including EBV post-transplant lymphoproliferative disorders (LPD, Hodgkin and non-Hodgkin lymphomas, nasopharyngeal carcinoma and Burkitt lymphoma. The range of expression of latent EBV antigens varies in these tumors, which influences how susceptible the tumors are to immunotherapeutic approaches. Tumors expressing type III latency, such as in LPD, express the widest array of EBV antigens making them the most susceptible to immunotherapy. Treatment strategies for EBV-related tumors include restoring normal cellular immunity by adoptive immunotherapy with EBV-specific T cells and targeting the malignant B cells with monoclonal antibodies. We review the current immunotherapies and future studies aimed at targeting EBV antigen expression in these tumors.

  18. Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris.

    Science.gov (United States)

    Liu, Pei-Feng; Hsieh, Yao-Dung; Lin, Ya-Ching; Two, Aimee; Shu, Chih-Wen; Huang, Chun-Ming

    2015-01-01

    Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The gram-positive and anaerobic Propionibacterium acnes (P. acnes) bacterium has been implicated in acne inflammation and pathogenesis. Therapies for acne vulgaris using antibiotics generally lack bacterial specificity, promote the generation of antibiotic-resistant bacterial strains, and cause adverse effects. Immunotherapy against P. acnes or its antigens (sialidase and CAMP factor) has been demonstrated to be effective in mice, attenuating P. acnes-induced inflammation; thus, this method may be applied to develop a potential vaccine targeting P. acnes for acne vulgaris treatment. This review summarizes reports describing the role of P. acnes in the pathogenesis of acne and various immunotherapy-based approaches targeting P. acnes, suggesting the potential effectiveness of immunotherapy for acne vulgaris as well as P. acnes-associated diseases.

  19. Cellular immunotherapy of cancer: an overview and future directions.

    Science.gov (United States)

    Tao, Ziqi; Li, Shuang; Ichim, Thomas E; Yang, Junbao; Riordan, Neil; Yenugonda, Venkata; Babic, Ivan; Kesari, Santosh

    2017-06-01

    The clinical success of checkpoint inhibitors has led to a renaissance of interest in cancer immunotherapies. In particular, the possibility of ex vivo expanding autologous lymphocytes that specifically recognize tumor cells has attracted much research and clinical trial interest. In this review, we discuss the historical background of tumor immunotherapy using cell-based approaches, and provide some rationale for overcoming current barriers to success of autologous immunotherapy. An overview of adoptive transfer of lymphocytes, tumor infiltrating lymphocytes and dendritic cell therapies is provided. We conclude with discussing the possibility of gene-manipulating immune cells in order to augment therapeutic activity, including silencing of the immune-suppressive zinc finger orphan nuclear receptor, NR2F6, as an attractive means of overcoming tumor-associated immune suppression.

  20. Melanoma immunotherapy: historical precedents, recent successes and future prospects.

    Science.gov (United States)

    Raaijmakers, Marieke I G; Rozati, Sima; Goldinger, Simone M; Widmer, Daniel S; Dummer, Reinhard; Levesque, Mitchell P

    2013-02-01

    The idea of cancer immunotherapy has been around for more than a century; however, the first immunotherapeutic ipilimumab, an anti-CTLA-4 antibody, has only recently been approved by the US FDA for melanoma. With an increasing understanding of the immune response, it is expected that more therapies will follow. This review aims to provide a general overview of immunotherapy in melanoma. We first explain the development of cancer immunotherapy more than a century ago and the general opinions about it over time. This is followed by a general overview of the immune reaction in order to give insight into the possible targets for therapy. Finally, we will discuss the current therapies for melanoma, their shortcomings and why it is important to develop patient stratification criteria. We conclude with an overview of recent discoveries and possible future therapies.

  1. Immunotherapy Approaches for Malignant Glioma From 2007 to 2009

    Science.gov (United States)

    Sampson, John H.

    2012-01-01

    Malignant glioma is a deadly disease for which there have been few therapeutic advances over the past century. Although previous treatments were largely unsuccessful, glioma may be an ideal target for immune-based therapy. Recently, translational research led to several clinical trials based on tumor immunotherapy to treat patients with malignant glioma. Here we review 17 recent glioma immunotherapy clinical trials, published over the past 3 years. Various approaches were used, including passive transfer of naked and radiolabeled antibodies, tumor antigen-specific peptide immunization, and the use of patient tumor cells with or without dendritic cells as vaccines. We compare and discuss the current state of the art of clinical immunotherapy treatment, as well as its limited successes, pitfalls, and future potential. PMID:20424975

  2. Sublingual immunotherapy for allergic rhinitis: where are we now?

    Science.gov (United States)

    Incorvaia, Cristoforo; Mauro, Marina; Ridolo, Erminia

    2015-01-01

    Sublingual immunotherapy (SLIT) was introduced in the 1980s as a safer option to subcutaneous immunotherapy and in the latest decade achieved significant advances. Its efficacy in allergic rhinitis is supported by a number of meta-analyses. The development of SLIT preparations in tablets to fulfill the requirements of regulatory agencies for quality of allergen extracts made available optimal products for grass-pollen-induced allergic rhinitis. Preparations of other allergens based on the same production methods are currently in progress. A notable outcome of SLIT, that is shared with subcutaneous immunotherapy, is the evident cost-effectiveness, showing significant cost savings as early as 3 months from starting the treatment, that become as high as 80% compared with drug treatment in the ensuing years.

  3. Gene therapy for carcinoma of the breast: Genetic immunotherapy

    International Nuclear Information System (INIS)

    Strong, Theresa V

    2000-01-01

    Advances in gene transfer technology have greatly expanded the opportunities for developing immunotherapy strategies for breast carcinoma. Genetic immunotherapy approaches include the transfer of genes encoding cytokines and costimulatory molecules to modulate immune function, as well as genetic immunization strategies which rely on the delivery of cloned tumor antigens. Improved gene transfer vectors, coupled with a better understanding of the processes that are necessary to elicit an immune response and an expanding number of target breast tumor antigens, have led to renewed enthusiasm that effective immunotherapy may be achieved. It is likely that immunotherapeutic interventions will find their greatest clinical application as adjuvants to traditional first-line therapies, targeting micrometastatic disease and thereby reducing the risk of cancer recurrence

  4. New modalities of cancer treatment for NSCLC: focus on immunotherapy

    International Nuclear Information System (INIS)

    Davies, Marianne

    2014-01-01

    Recent advances in the understanding of immunology and antitumor immune responses have led to the development of new immunotherapies, including vaccination approaches and monoclonal antibodies that inhibit immune checkpoint pathways. These strategies have shown activity in melanoma and are now being tested in lung cancer. The antibody drugs targeting cytotoxic T-lymphocyte-associated antigen-4 and programmed cell death protein-1 immune checkpoint pathways work by restoring immune responses against cancer cells, and are associated with unconventional response patterns and immune-related adverse events as a result of their mechanism of action. As these new agents enter the clinic, nurses and other health care providers will require an understanding of the unique efficacy and safety profiles with immunotherapy to optimize potential patient benefits. This paper provides a review of the new immunotherapeutic agents in development for lung cancer, and strategies for managing patients on immunotherapy

  5. Immunotherapy for Urothelial Carcinoma: Current Status and Perspectives

    International Nuclear Information System (INIS)

    Kitamura, Hiroshi; Tsukamoto, Taiji

    2011-01-01

    Intravesical instillation of bacillus Calmette Guérin (BCG) for the treatment of urothelial carcinoma (UC) of the bladder is based on the BCG-induced immune response, which eradicates and prevents bladder cancer. The results of recent studies have suggested that not only major histocompatibility complex (MHC)-nonrestricted immune cells such as natural killer cells, macrophages, neutrophils, etc., but also MHC-restricted CD8 + T cells play an important role and are one of the main effectors in this therapy. Better understanding of the mechanism of BCG immunotherapy supports the idea that active immunotherapy through its augmented T cell response can have great potential for the treatment of advanced UC. In this review, progress in immunotherapy for UC is discussed based on data from basic, translational and clinical studies. We also review the escape mechanism of cancer cells from the immune system, and down-regulation of MHC class I molecules

  6. Oral immunotherapy for food allergy: mechanisms and role in management.

    Science.gov (United States)

    Nowak-Węgrzyn, A; Albin, S

    2015-02-01

    With the emergence of food allergy as an important public health problem, it has become clear that there is an unmet need in regard to treatment. In particular, IgE-mediated food allergy that is associated with risk of fatal anaphylaxis has been the subject of multiple studies in the past decade. The growing body of evidence derived from multiple centres and various study designs indicates that for IgE-mediated food allergy, immunomodulation through food immunotherapy is possible; however, the extent of protection afforded by such treatment is highly variable. At this time, the capacity for food immunotherapy to restore permanent tolerance to food has not been demonstrated conclusively. This review will discuss these topics as they apply to the most important studies of food oral immunotherapy. © 2014 John Wiley & Sons Ltd.

  7. Targeted immunotherapy in acute myeloblastic leukemia: from animals to humans.

    Science.gov (United States)

    Robin, Marie; Schlageter, Marie-Hélène; Chomienne, Christine; Padua, Rose-Ann

    2005-10-01

    Immunity against acute myeloid leukemia (AML) is demonstrated in humans by the graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation. Specific leukemic antigens have progressively been discovered and circulating specific T lymphocytes against Wilms tumor antigen, proteinase peptide or fusion-proteins produced from aberrant oncogenic chromosomal translocations have been detected in leukemic patients. However, due to the fact that leukemic blasts develop various escape mechanisms, antileukemic specific immunity is not able to control leukemic cell proliferation. The aim of immunotherapy is to overcome tolerance and boost immunity to elicit an efficient immune response against leukemia. We review different immunotherapy strategies tested in preclinical animal models of AML and the human trials that spurred from encouraging results obtained in animal models, demonstrate the feasibility of immunotherapy in AML patients.

  8. IMMUNOTHERAPY FOR EPSTEIN-BARR VIRUS-RELATED LYMPHOMAS

    Directory of Open Access Journals (Sweden)

    Helen Heslop

    2009-11-01

    Full Text Available

    Latent EBV infection is associated with several malignancies, including EBV post-transplant lymphoproliferative disorders (LPD, Hodgkin and non-Hodgkin lymphomas, nasopharyngeal carcinoma and Burkitt lymphoma. The range of expression of latent EBV antigens varies in these tumors, which influences how susceptible the tumors are to immunotherapeutic approaches. Tumors expressing type III latency, such as in LPD, express the widest array of EBV antigens making them the most susceptible to immunotherapy. Treatment strategies for EBV-related tumors include restoring normal cellular immunity by adoptive immunotherapy with EBV-specific T cells and targeting the malignant B cells with monoclonal antibodies. We review the current immunotherapies and future studies aimed at targeting EBV antigen expression in these tumors.

  9. Immunotherapy with rituximab in follicular lymphomas.

    Science.gov (United States)

    Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

    2011-04-01

    Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

  10. Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2012-01-01

    Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.

  11. Allergen-specific immunotherapy and risk of autoimmune disease

    DEFF Research Database (Denmark)

    Linneberg, Allan; Madsen, Flemming; Skaaby, Tea

    2012-01-01

    After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic.......After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic....

  12. Allergen immunotherapy for the prevention of allergic disease

    DEFF Research Database (Denmark)

    Dhami, Sangeeta; Nurmatov, Ulugbek; Halken, Susanne

    2016-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the pre......BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT...

  13. Reconceptualizing cancer immunotherapy based on plant production systems

    Science.gov (United States)

    Hefferon, Kathleen

    2017-01-01

    Plants can be used as inexpensive and facile production platforms for vaccines and other biopharmaceuticals. More recently, plant-based biologics have expanded to include cancer immunotherapy agents. The following review describes the current state of the art for plant-derived strategies to prevent or reduce cancers. The review discusses avenues taken to prevent infection by oncogenic viruses, solid tumors and lymphomas. Strategies including cancer vaccines, monoclonal antibodies and virus nanoparticles are described, and examples are provided. The review ends with a discussion of the implications of plant-based cancer immunotherapy for developing countries. PMID:28884013

  14. Immunotherapies: Exploiting the Immune System for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Jeffrey Koury

    2018-01-01

    Full Text Available Cancer is a condition that has plagued humanity for thousands of years, with the first depictions dating back to ancient Egyptian times. However, not until recent decades have biological therapeutics been developed and refined enough to safely and effectively combat cancer. Three unique immunotherapies have gained traction in recent decades: adoptive T cell transfer, checkpoint inhibitors, and bivalent antibodies. Each has led to clinically approved therapies, as well as to therapies in preclinical and ongoing clinical trials. In this review, we outline the method by which these 3 immunotherapies function as well as any major immunotherapeutic drugs developed for treating a variety of cancers.

  15. Personalized adoptive immunotherapy for patients with EBVassociated tumors and complications

    DEFF Research Database (Denmark)

    Bieling, Maren; Tischer, Sabine; Kalinke, Ulrich

    2018-01-01

    -immortalized B cells transduced with soluble HLA-A*03:01, sorted using different epitope prediction tools and eleven candidates were preselected. T2 and Flex-T peptide-binding and dissociation assays confirmed the stability of peptide-MHC complexes. Their immunogenicity and clinical relevance were evaluated......-toxic immunotherapy to effectively prevent or treat these complications. To improve immunotherapy and immunomonitoring this study aimed at identifying and evaluating naturally processed and presented HLA-A*03:01-restricted EBV-CTL epitopes as immunodominant targets. More than 15000 peptides were sequenced from EBV...

  16. Porous silicon advances in drug delivery and immunotherapy.

    Science.gov (United States)

    Savage, David J; Liu, Xuewu; Curley, Steven A; Ferrari, Mauro; Serda, Rita E

    2013-10-01

    Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Allergen-specific immunotherapy in asthmatic children: from the basis to clinical applications.

    Science.gov (United States)

    Aryan, Zahra; Compalati, Enrico; Comapalati, Enrico; Canonica, Giorgio Walter; Rezaei, Nima

    2013-06-01

    Atopic asthma in childhood with the tendency to persist into adult life is an important issue in pediatrics. Allergen-specific immunotherapy (SIT) is the only curative treatment option for these children, being directed to the causes of the disease. The Th2 phenotype is a predominant immunological pattern in atopic asthma and SIT leads to apoptosis/anergy of T cells and induces immune-regulatory responses and immune deviation towards Th1. Many factors can affect the safety and efficacy of SIT, such as pattern of sensitization, allergy vaccine (allergen extracts, adjuvants and conjugated molecules), route of administration (subcutaneous or sublingual) and different treatment schedules. Overall, asthma symptoms and medication scores usually decrease following a SIT course and the most common observed side effects are restricted to local swelling, erythema and pruritus. Compared with conventional pharmacotherapy, SIT may be more cost effective, providing a benefit after discontinuation and a steroid-sparing effect. In addition, it can prevent new sensitizations in monosensitized asthmatic children. Microbial supplements such as probiotics, immunomodulatory substances like anti-IgE/leukotrienes, antibodies and newer allergen preparations such as recombinant forms have been tested to improve the efficacy and safety of SIT with inconclusive results. In conclusion, SIT provides an appropriate solution for childhood asthma that should be employed more often in clinical practice. Further studies are awaited to improve current knowledge regarding the mechanisms behind SIT and determine the most appropriate materials and schedule of immunotherapy for children with asthma.

  18. Toll-like receptors as targets for allergen immunotherapy.

    Science.gov (United States)

    Aryan, Zahra; Rezaei, Nima

    2015-12-01

    Toll-like receptors (TLRs) are novel and promising targets for allergen immunotherapy. Bench studies suggest that TLR agonists reduce Th2 responses and ameliorate airway hyper-responsiveness. In addition, clinical trials are at initial phases to evaluate the safety and efficacy of TLR agonists for the allergen immunotherapy of patients with allergic rhinitis and asthma. (Figure is included in full-text article.) To date, two allergy vaccine-containing TLR agonists have been investigated in clinical trials; Pollinex Quattro and AIC. The former contains monophosphoryl lipid, a TLR4 agonist and the latter contains, CpG motifs activating the TLR9 cascade. Preseasonal subcutaneous injection of both of these allergy vaccines has been safe and efficacious in control of nasal symptoms of patients with allergic rhinitis. CRX-675 (a TLR4 agonist), AZD8848 (a TLR7 agonist), VTX-1463 (a TLR8 agonist) and 1018 ISS and QbG10 (TLR9 agonists) are currently in clinical development for allergic rhinitis and asthma. TLR agonists herald promising results for allergen immunotherapy of patients with allergic rhinitis and asthma. Future research should be directed at utilizing these agents for immunotherapy of food allergy (for instance, peanut allergy) as well.

  19. Improving the clinical impact of biomaterials in cancer immunotherapy

    Science.gov (United States)

    Gammon, Joshua M.; Dold, Neil M.; Jewell, Christopher M.

    2016-01-01

    Immunotherapies for cancer have progressed enormously over the past few decades, and hold great promise for the future. The successes of these therapies, with some patients showing durable and complete remission, demonstrate the power of harnessing the immune system to eradicate tumors. However, the effectiveness of current immunotherapies is limited by hurdles ranging from immunosuppressive strategies employed by tumors, to inadequate specificity of existing therapies, to heterogeneity of disease. Further, the vast majority of approved immunotherapies employ systemic delivery of immunomodulators or cells that make addressing some of these challenges more difficult. Natural and synthetic biomaterials–such as biocompatible polymers, self-assembled lipid particles, and implantable biodegradable devices–offer unique potential to address these hurdles by harnessing the benefits of therapeutic targeting, tissue engineering, co-delivery, controlled release, and sensing. However, despite the enormous investment in new materials and nanotechnology, translation of these ideas to the clinic is still an uncommon outcome. Here we review the major challenges facing immunotherapies and discuss how the newest biomaterials and nanotechnologies could help overcome these challenges to create new clinical options for patients. PMID:26871948

  20. Prospects for immunotherapy of MHC class I-deficient tumours

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2003-01-01

    Roč. 49, č. 3 (2003), s. 95-99 ISSN 0015-5500 Institutional research plan: CEZ:AV0Z5052915 Keywords : MHC class I * immunotherapy Subject RIV: FD - Oncology ; Hematology Impact factor: 0.527, year: 2003

  1. Allergen Immunotherapy (AIT): a prototype of Precision Medicine

    NARCIS (Netherlands)

    Canonica, G. W.; Bachert, C.; Hellings, P.; Ryan, D.; Valovirta, E.; Wickman, M.; de Beaumont, O.; Bousquet, J.

    2015-01-01

    Precision medicine is a medical model aiming to deliver customised healthcare - with medical decisions, practices, and/or products tailored to the individual patient informed but not directed by guidelines. Allergen immunotherapy has unique immunological rationale, since the approach is tailored to

  2. Liposome-based synthetic long peptide vaccines for cancer immunotherapy

    NARCIS (Netherlands)

    Varypataki, E.M.

    2016-01-01

    Synthetic long peptides (SLP) derived from cancer-associated antigens hold great promise as well-defined antigens for cancer immunotherapy. Clinical studies showed that SLP vaccines have functional potency when applied to pre-malignant stage patients, but need to be improved for use as a therapeutic

  3. Challenges in the implementation of EAACI guidelines on allergen immunotherapy

    DEFF Research Database (Denmark)

    Bonertz, A; Roberts, G C; Hoefnagel, M

    2018-01-01

    Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulator...

  4. T-cell apoptosis in asthmatics before and after immunotherapy

    International Nuclear Information System (INIS)

    Abd El All, L.M.A

    2008-01-01

    This study aimed to observe some of the mechanisms of allergen specific immunotherapy and to see if the idea of delayed Th 2 lymphocytes apoptosis is a contributing factor in asthma pathogenesis that could be corrected by immunotherapy. The study was conducted on 40 persons 30 asthmatic patients, 10 healthy control groups. After taking full history and clinical examination all subjects was submitted to the following assays: 1- Measuring of the CD 9 5 on T lymphocytes in fresh blood samples using flow cytometric analysis. 2- Measuring level of lgE (nephlometer).3-Measuring level of IL-4 (ELISA).4-Measuring level of IFN-gamma (ELISA). CD 9 5 was significantly increased in asthmatic patients denoting up regulation of the receptor on T-lymphocytes in asthmatics . The percent of CD 9 5 was decreased in treated asthmatic subjects with no statistical significant difference. Total lgE and serum IL-4 were significantly increased in asthmatics denoting allergic nature, these levels were decreased after the immunotherapy confirming a relation ship between the application course duration of the immunotherapy and the relief of the inflammatory symptoms and remolding.

  5. Immunotherapy targeting immune check-point(s) in brain metastases.

    Science.gov (United States)

    Di Giacomo, Anna Maria; Valente, Monica; Covre, Alessia; Danielli, Riccardo; Maio, Michele

    2017-08-01

    Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype. These observations remain to be validated in larger clinical trials eventually designed also to address the efficacy of therapeutic mAb to immune check-point(s) within multimodality therapies for brain metastases. Noteworthy, the initial proofs of efficacy on immunotherapy in central nervous system metastases are already fostering clinical trials investigating its therapeutic potential also in primary brain tumors. We here review ongoing immunotherapeutic approaches to brain metastases and primary brain tumors, and the foreseeable strategies to overcome their main biologic hurdles and clinical challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Allergen-specific immunotherapy of Hymenoptera venom allergy

    DEFF Research Database (Denmark)

    Schiener, Maximilian; Graessel, Anke; Ollert, Markus

    2017-01-01

    by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy...

  7. The current state of recombinant allergens for immunotherapy

    DEFF Research Database (Denmark)

    Pauli, Gabrielle; Malling, H-J

    2010-01-01

    Subcutaneous immunotherapy is a well documented treatment of allergic rhinitis and asthma. The majority of the disadvantages of the treatment are related to the poor quality of the natural allergen extracts which can contain varying amounts of individual allergens including allergens to which...

  8. Mycobacterium bovis endophthalmitis from BCG immunotherapy for bladder cancer

    NARCIS (Netherlands)

    Gerbrandy, S. J. F.; Schreuders, L. C.; de Smet, M. D.

    2008-01-01

    BACKGROUND: We report a patient who developed BCG endophthalmitis after BCG immunotherapy for bladder cancer. Comparison of this case with 2 other reported cases reveals a similar pattern of elderly, debilitated and immunocompromised patients with poor response to systemic antituberculous therapy in

  9. Immunotherapy in Gynecologic Cancers: Are We There Yet?

    Science.gov (United States)

    Pakish, Janelle B; Jazaeri, Amir A

    2017-08-24

    Immune-targeted therapies have demonstrated durable responses in many tumor types with limited treatment options and poor overall prognosis. This has led to enthusiasm for expanding such therapies to other tumor types including gynecologic malignancies. The use of immunotherapy in gynecologic malignancies is in the early stages and is an active area of ongoing clinical research. Both cancer vaccines and immune checkpoint inhibitor therapy continue to be extensively studied in gynecologic malignancies. Immune checkpoint inhibitors, in particular, hold promising potential in specific subsets of endometrial cancer that express microsatellite instability. The key to successful treatment with immunotherapy involves identification of the subgroup of patients that will derive benefit. The number of ongoing trials in cervical, ovarian, and endometrial cancer will help to recognize these patients and make treatment more directed. Additionally, a number of studies are combining immunotherapy with standard treatment options and will help to determine combinations that will enhance responses to standard therapy. Overall, there is much enthusiasm for immunotherapy approaches in gynecologic malignancies. However, the emerging data shows that with the exception of microsatellite unstable tumors, the use of single-agent immune checkpoint inhibitors is associated with response rates of 10-15%. More effective and likely combinatorial approaches are needed and will be informed by the findings of ongoing trials.

  10. Perspectives on allergen-specific immunotherapy in childhood

    DEFF Research Database (Denmark)

    Calderon, M A; Gerth van Wijk, R; Eichler, I

    2012-01-01

    -specific immunotherapy in childhood. Unmet needs are identified. To fill the gaps and to bridge the different points of view, recommendations are made to researchers, to scientific and patient organizations and to regulators and ethical committees. Working together for the benefit of the community is essential...

  11. Dendritic cell-tumor cell hybrids and immunotherapy

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André

    2011-01-01

    Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...

  12. Tumor immunotherapy : clinics of cytokines and monoclonal antibodies

    NARCIS (Netherlands)

    Nieken, Judith

    1999-01-01

    Tumor immunotherapy is defines as treatment that induces anti-tumor responses via the modulation of both cellular and homoral components of the host immune system. Its concept is based on hte assumption that tumor cells express unique protiens, so-calles tumor antigens, that can be identified as

  13. New modalities of cancer treatment for NSCLC: focus on immunotherapy

    Directory of Open Access Journals (Sweden)

    Davies M

    2014-02-01

    Full Text Available Marianne Davies Smilow Cancer Hospital at Yale-New Haven Hospital, New Haven, CT, USA Abstract: Recent advances in the understanding of immunology and antitumor immune responses have led to the development of new immunotherapies, including vaccination approaches and monoclonal antibodies that inhibit immune checkpoint pathways. These strategies have shown activity in melanoma and are now being tested in lung cancer. The antibody drugs targeting cytotoxic T-lymphocyte-associated antigen-4 and programmed cell death protein-1 immune checkpoint pathways work by restoring immune responses against cancer cells, and are associated with unconventional response patterns and immune-related adverse events as a result of their mechanism of action. As these new agents enter the clinic, nurses and other health care providers will require an understanding of the unique efficacy and safety profiles with immunotherapy to optimize potential patient benefits. This paper provides a review of the new immunotherapeutic agents in development for lung cancer, and strategies for managing patients on immunotherapy. Keywords: immunotherapy, lung cancer, vaccination, nivolumab, ipilimumab, nursing

  14. Preliminary clinical trial of immunotherapy for malignant glioma.

    Science.gov (United States)

    Ingram, M; Shelden, C H; Jacques, S; Skillen, R G; Bradley, W G; Techy, G B; Freshwater, D B; Abts, R M; Rand, R W

    1987-10-01

    An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

  15. Allergen immunotherapy for allergic rhinoconjunctivitis : protocol for a systematic review

    NARCIS (Netherlands)

    Dhami, Sangeeta; Nurmatov, Ulugbek; Roberts, Graham; Pfaar, Oliver; Muraro, Antonella; Ansotegui, Ignacio J; Calderon, Moises; Cingi, Cemal; Demoly, Pascal; Durham, Stephen; van Wijk, Ronald Gerth; Halken, Susanne; Hamelmann, Eckard; Hellings, Peter; Jacobsen, Lars; Knol, Edward; Linnemann, Desiree Larenas; Lin, Sandra; Maggina, Vivian; Oude-Elberink, Hanneke; Pajno, Giovanni; Panwankar, Ruby; Pastorello, Elideanna; Pitsios, Constantinos; Rotiroti, Giuseppina; Timmermans, Frans; Tsilochristou, Olympia; Varga, Eva-Maria; Wilkinson, Jamie; Williams, Andrew; Worm, Margitta; Zhang, Luo; Sheikh, Aziz

    2016-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT

  16. Allergen immunotherapy for allergic asthma: Protocol for a systematic review

    NARCIS (Netherlands)

    Dhami, S. (Sangeeta); Nurmatov, U. (Ulugbek); I. Agache; S. Lau (Susanne); Muraro, A. (Antonella); M. Jutel (M.); G. Roberts; C.A. Akdis; M. Bonini (Matteo); M. Calderon (Moises); T.B. Casale (Thomas); Cavkaytar, O. (Ozlem); L. Cox (Linda); P. Demoly; Flood, B. (Breda); Hamelmann, E. (Eckard); Izuhara, K. (Kenji); O. Kalayci; J. Kleine-Tebbe (Jörg); A. Nieto (Antonio); N. Papadopoulos; O. Pfaar (Oliver); L. Rosenwasser (Lanny); D. Ryan (Dermot); C.B. Schmidt-Weber; S.J. Szefler; U. Wahn (Ulrich); R. Gerth van Wijk (Roy); Wilkinson, J. (Jamie); A. Sheikh (Aziz)

    2016-01-01

    textabstractBackground: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of

  17. Minimally invasive diagnostics and immunotherapy of lung cancer

    NARCIS (Netherlands)

    Talebian-Yazdi, M.

    2017-01-01

    This thesis deals with aspects of diagnostics and immunotherapy of lung cancer. The first aim of this thesis is to investigate how the implementation of minimally invasive endoscopic ultrasound techniques (EUS and EBUS) in the staging algorithm of NSCLC can be optimized. The second aim of this

  18. Sublingual immunotherapy for the treatment of allergies | Schellack ...

    African Journals Online (AJOL)

    The treatment of allergies often involves pharmacological therapy and recommendations by healthcare workers that the allergen should be avoided. Allergen-specific immunotherapy has emerged as an alternative to effectively decrease the immunoglobulin (Ig) E:IgG4 ratio. Two routes of administration are described, ...

  19. Immunology and Immunotherapy of high grade cervical lesions and cancer

    NARCIS (Netherlands)

    Vos van Steenwijk, Peggy Jacqueline de

    2015-01-01

    Cervical cancer is caused by the human papillomavirus (HPV). The immune system plays an important role in the protection against HPV and failure of the immune system can lead to the development of cervical cancer. Immunotherapy aims at the restoration of an effective anti-tumour immunity. This

  20. Immunotherapy for head and neck cancer patients: shifting the balance

    NARCIS (Netherlands)

    Turksma, A.W.; Braakhuis, B.J.M.; Bloemena, E.; Meijer, C.J.L.M.; Leemans, C.R.; Hooijberg, E.

    2013-01-01

    Head and neck squamous cell carcinoma is the sixth most common cancer in the western world. Over the last few decades little improvement has been made to increase the relatively low 5-year survival rate. This calls for novel and improved therapies. Here, we describe opportunities in immunotherapy

  1. Seasonal versus perennial immunotherapy: evaluation after three years of treatment.

    Science.gov (United States)

    Muñoz Lejarazu, D; Bernaola, G; Fernández, E; Audícana, M; Ventas, P; Martín, S; Fernández de Corres, L

    1993-01-01

    We have performed a comparative study to evaluate seasonal and perennial schedules after 3 years of immunotherapy. Sixty patients suffering from rhinitis and/or asthma due to grass pollen sensitization were randomly allocated to receive a semi-depot extract of Phleum pratense according to a perennial or seasonal schedule. The last year of the study, 14 patients were recruited as a control group without immunotherapy. The cumulative dose was 602 BU in the perennial group and 372 BU in the seasonal group. The frequency and severity of side-effects were similar and very low in both treated groups. The IgE level was significantly lower after perennial immunotherapy at the end of the first 2 years. A seasonal decrease in specific IgG levels was observed in patients who interrupted immunotherapy, while this was not observed in patients under the perennial schedule. Symptoms and medication scores did not show differences between groups. Nevertheless, we found a significant difference between treated patients and the control group.

  2. [Immunotherapy in epithelial ovarian carcinoma: hope and reality].

    Science.gov (United States)

    Lavoué, V; Foucher, F; Henno, S; Bauville, E; Catros, V; Cabillic, F; Levêque, J

    2014-03-01

    Epithelial ovarian carcinoma (EOC) has a worst prognosis with little progress in terms of survival for the last two decades. Immunology received little interest in EOC in the past, but now appears very important in the natural history of this cancer. This review is an EOC immunology state of art and focuses on the place of immunotherapy in future. A systematic review of published studies was performed. Medline baseline interrogation was performed with the following keywords: "Ovarian carinoma, immunotherapy, T-lymphocyte, regulator T-lymphocyte, dendritic cells, macrophage, antigen, chemotherapy, surgery, clinical trials". Identified publications (English or French) were assessed for the understanding of EOC immunology and the place of conventional treatment and immunotherapy strategy. Intratumoral infiltration by immune cells is a strong prognotic factor in EOC. Surgery and chemotherapy in EOC decrease imunosuppression in patients. The antitumoral immunity is a part of the therapeutic action of surgery and chemotherapy. Until now, immunotherapy gave some disappointing results, but the new drugs that target the tolerogenic tumoral microenvironnement rise and give a new hope in the treatment of cancer. Immunology controls the EOC natural history. The modulation of immunosuppressive microenvironment associated with the stimulation of antitumoral immunity could be the next revolution in the treatment of cancer. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. Allergen immunotherapy for IgE-mediated food allergy

    DEFF Research Database (Denmark)

    Dhami, Sangeeta; Nurmatov, Ulugbek; Pajno, Giovanni Battista

    2016-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated food allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in IgE-mediated food...

  4. Immunotherapy of Head and Neck Cancer: Current and Future Considerations

    Directory of Open Access Journals (Sweden)

    Alexander D. Rapidis

    2009-01-01

    Full Text Available Patients with head and neck squamous cell carcinoma (HNSCC are at considerable risk for death, with 5-year relative survival rates of approximately 60%. The profound multifaceted deficiencies in cell-mediated immunity that persist in most patients after treatment may be related to the high rates of treatment failure and second primary malignancies. Radiotherapy and chemoradiotherapy commonly have severe acute and long-term side effects on immune responses. The development of immunotherapies reflects growing awareness that certain immune system deficiencies specific to HNSCC and some other cancers may contribute to the poor long-term outcomes. Systemic cell-mediated immunotherapy is intended to activate the entire immune system and mount a systemic and/or locoregional antitumor response. The delivery of cytokines, either by single cytokines, for example, interleukin-2, interleukin-12, interferon-, interferon-, or by a biologic mix of multiple cytokines, such as IRX-2, may result in tumor rejection and durable immune responses. Targeted immunotherapy makes use of monoclonal antibodies or vaccines. All immunotherapies for HNSCC except cetuximab remain investigational, but a number of agents whose efficacy and tolerability are promising have entered phase 2 or phase 3 development.

  5. Specific immunotherapy in renal cancer: a systematic review.

    Science.gov (United States)

    Hirbod-Mobarakeh, Armin; Gordan, Hesam Addin; Zahiri, Zahra; Mirshahvalad, Mohammad; Hosseinverdi, Sima; Rini, Brian I; Rezaei, Nima

    2017-02-01

    Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration). We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58-0.89, p = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients undergoing specific immunotherapy

  6. Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions

    Directory of Open Access Journals (Sweden)

    Shilpa Gupta

    2017-01-01

    Full Text Available Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC. Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1 inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for firstline platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC.

  7. IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent head and neck cancer

    International Nuclear Information System (INIS)

    Zwicker, Felix; Roeder, Falk; Thieke, Christian; Timke, Carmen; Huber, Peter E.; Deutsches Krebsforschungszentrum; Muenter, Marc W.; Debus, Juergen

    2011-01-01

    Purpose: In this retrospective investigation, the outcome and toxicity after reirradiation with concurrent cetuximab immunotherapy of recurrent head and neck cancer (HNC) in patients who had contraindications to platinum-based chemotherapy were analyzed. Materials and Methods: Ten patients with locally advanced recurrent HNC were retrospectively evaluated. In 9 cases, histology was squamous cell carcinoma, in one case adenoid cystic carcinoma. External beam radiotherapy was part of the initial treatment in all cases. Reirradiation was carried out using step-and-shoot intensity-modulated radiotherapy (IMRT) with a median dose of 50.4 Gy. Cetuximab was applied as loading dose (400 mg/m 2 ) 1 week prior to reirradiation and then weekly concurrently with radiotherapy (250 mg/m 2 ). Results: The median overall survival time after initiation of reirradiation was 7 months; the 1-year overall survival (OS) rate was 40%. Local failure was found in 3 patients, resulting in a 1-year local control (LC) rate of 61%. The 1-year locoregional control (LRC) rate was 44%, while the 1-year distant metastasis-free survival (DMFS) was 75%. Acute hematological toxicity was not observed in the group. Severe acute toxicity included one fatal infield arterial bleeding and one flap necrosis. Severe late toxicities were noted in 2 patients: fibrosis of the temporomandibular joint in 1 patient and stenosis of the cervical esophagus in another. Conclusions: IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent HNC is feasible with acceptable acute toxicity. Further investigations are necessary to determine the clinical role of this therapy concept. (orig.)

  8. IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zwicker, Felix; Roeder, Falk; Thieke, Christian; Timke, Carmen; Huber, Peter E. [Heidelberg Univ. (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Div. of Radiation Oncology; Muenter, Marc W.; Debus, Juergen [Heidelberg Univ. (Germany). Dept. of Radiation Oncology

    2011-01-15

    Purpose: In this retrospective investigation, the outcome and toxicity after reirradiation with concurrent cetuximab immunotherapy of recurrent head and neck cancer (HNC) in patients who had contraindications to platinum-based chemotherapy were analyzed. Materials and Methods: Ten patients with locally advanced recurrent HNC were retrospectively evaluated. In 9 cases, histology was squamous cell carcinoma, in one case adenoid cystic carcinoma. External beam radiotherapy was part of the initial treatment in all cases. Reirradiation was carried out using step-and-shoot intensity-modulated radiotherapy (IMRT) with a median dose of 50.4 Gy. Cetuximab was applied as loading dose (400 mg/m{sup 2}) 1 week prior to reirradiation and then weekly concurrently with radiotherapy (250 mg/m{sup 2}). Results: The median overall survival time after initiation of reirradiation was 7 months; the 1-year overall survival (OS) rate was 40%. Local failure was found in 3 patients, resulting in a 1-year local control (LC) rate of 61%. The 1-year locoregional control (LRC) rate was 44%, while the 1-year distant metastasis-free survival (DMFS) was 75%. Acute hematological toxicity was not observed in the group. Severe acute toxicity included one fatal infield arterial bleeding and one flap necrosis. Severe late toxicities were noted in 2 patients: fibrosis of the temporomandibular joint in 1 patient and stenosis of the cervical esophagus in another. Conclusions: IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent HNC is feasible with acceptable acute toxicity. Further investigations are necessary to determine the clinical role of this therapy concept. (orig.)

  9. 13-year overview of serious adverse drug reactions following subcutaneous specific immunotherapy with a chemically modified allergen preparation.

    Science.gov (United States)

    Distler, Andreas; Pappelendam, Debbie

    The Paul-Ehrlich-Institut (PEI) published an analysis of reports of adverse drug reactions (ADRs) in 2001 with test and therapy allergens from the period from 1991 to 2000. Possible risk factors were evaluated for the ADR reports classified as "serious". During the analyzed period, modified semi-depot preparations (allergoids) induced between 0.01 % and 0.0005 % serious systemic reactions, i. e. one serious ADR occurred in 10,000 to 200,000 injections. No information was provided regarding the respective incidences in relation to the individual companies or preparations. Within the scope of a 13-year analysis (2001-2013), the serious ADRs were analysed at HAL for the allergoid preparations PURETHAL® Pollen and Mites. As in the analysis of PEI, the frequency of serious ADRs was based on the estimated number of administered injections. A total of 46 cases with serious ADRs were received. In 26 % of the cases, a serious ADR occurred during initial treatment after the first injection. In 82.6 % of the cases, the serious ADR occurred within the 30-minute observation period in the practice. Adrenaline was administered as emergency treatment in seven cases. Hospitalisations were initiated by the treating physician or by patients themselves in 45 cases. The duration of the hospital stay varied from a few hours up to three days for further monitoring. Serious ADRs occurred in 11 cases with mites and in 35 cases with pollen. If it is assumed that there are six injections in each vial, this yields an incidence of 0.00061 % (1 : 164,000). The frequency with mites (0.00093 %) was slightly higher than with pollen (0.00055 %). The allergoid preparations (pollen and mite allergens) showed a very low risk of serious ADRs, which was close to the lower level of incidence of 0.0005 % for allergoid preparations published by the PEI.

  10. NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives

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    Remy Thomas

    2018-05-01

    Full Text Available NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancer-testis antigen (CTAs with re-expression in numerous cancer types. Its ability to elicit spontaneous humoral and cellular immune responses, together with its restricted expression pattern, have rendered it a good candidate target for cancer immunotherapy. In this review, we provide background information on NY-ESO-1 expression and function in normal and cancerous tissues. Furthermore, NY-ESO-1-specific immune responses have been observed in various cancer types; however, their utility as biomarkers are not well determined. Finally, we describe the immune-based therapeutic options targeting NY-ESO-1 that are currently in clinical trial. We will highlight the recent advancements made in NY-ESO-1 cancer vaccines, adoptive T cell therapy, and combinatorial treatment with checkpoint inhibitors and will discuss the current trends for future NY-ESO-1 based immunotherapy. Cancer treatment has been revolutionized over the last few decades with immunotherapy emerging at the forefront. Immune-based interventions have shown promising results, providing a new treatment avenue for durable clinical responses in various cancer types. The majority of successful immunotherapy studies have been reported in liquid cancers, whereas these approaches have met many challenges in solid cancers. Effective immunotherapy in solid cancers is hampered by the complex, dynamic tumor microenvironment that modulates the extent and phenotype of the antitumor immune response. Furthermore, many solid tumor-associated antigens are not private but can be found in normal somatic tissues, resulting in minor to detrimental off-target toxicities. Therefore, there is an ongoing effort to identify tumor-specific antigens to target using various immune-based modalities. CTAs are considered good candidate targets for immunotherapy as they are characterized by a restricted expression in normal somatic tissues

  11. MHC Intratumoral Heterogeneity May Predict Cancer Progression and Response to Immunotherapy

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    Irene Romero

    2018-01-01

    Full Text Available An individual tumor can present intratumoral phenotypic heterogeneity, containing tumor cells with different phenotypes that do not present irreversible genetic alterations. We have developed a mouse cancer model, named GR9, derived from a methylcholanthrene-induced fibrosarcoma that was adapted to tissue culture and cloned into different tumor cell lines. The clones showed diverse MHC-I phenotypes, ranging from highly positive to weakly positive MHC-I expression. These MHC-I alterations are due to reversible molecular mechanisms, because surface MHC-I could be recovered by IFN-γ treatment. Cell clones with high MHC-I expression demonstrated low local oncogenicity and high spontaneous metastatic capacity, whereas MHC-I-low clones showed high local oncogenicity and no spontaneous metastatic capacity. Although MHC-I-low clones did not metastasize, they produced MHC-I-positive dormant micrometastases controlled by the host immune system, i.e., in a state of immunodormancy. The metastatic capacity of each clone was directly correlated with the host T-cell subpopulations; thus, a strong decrease in cytotoxic and helper T lymphocytes was observed in mice with numerous metastases derived from MHC-I positive tumor clones but a strong increase was observed in those with dormant micrometastases. Immunotherapy was administered to the hosts after excision of the primary tumor, producing a recovery in their immune status and leading to the complete eradication of overt spontaneous metastases or their decrease. According to these findings, the combination of MHC-I surface expression in primary tumor and metastases with host T-cell subsets may be a decisive indicator of the clinical outcome and response to immunotherapy in metastatic disease, allowing the identification of responders to this approach.

  12. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function

    International Nuclear Information System (INIS)

    Veltman, Joris D; Lambers, Margaretha EH; Nimwegen, Menno van; Hendriks, Rudi W; Hoogsteden, Henk C; Aerts, Joachim GJV; Hegmans, Joost PJJ

    2010-01-01

    Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells that accumulates in tumour-bearing hosts. These cells are induced by tumour-derived factors (e.g. prostaglandins) and have a critical role in immune suppression. MDSC suppress T and NK cell function via increased expression of arginase I and production of reactive oxygen species (ROS) and nitric oxide (NO). Immune suppression by MDSC was found to be one of the main factors for immunotherapy insufficiency. Here we investigate if the in vivo immunoregulatory function of MDSC can be reversed by inhibiting prostaglandin synthesis by specific COX-2 inhibition focussing on ROS production by MDSC subtypes. In addition, we determined if dietary celecoxib treatment leads to refinement of immunotherapeutic strategies. MDSC numbers and function were analysed during tumour progression in a murine model for mesothelioma. Mice were inoculated with mesothelioma tumour cells and treated with cyclooxygenase-2 (COX-2) inhibitor celecoxib, either as single agent or in combination with dendritic cell-based immunotherapy. We found that large numbers of infiltrating MDSC co-localise with COX-2 expression in those areas where tumour growth takes place. Celecoxib reduced prostaglandin E2 levels in vitro and in vivo. Treatment of tumour-bearing mice with dietary celecoxib prevented the local and systemic expansion of all MDSC subtypes. The function of MDSC was impaired as was noticed by reduced levels of ROS and NO and reversal of T cell tolerance; resulting in refinement of immunotherapy. We conclude that celecoxib is a powerful tool to improve dendritic cell-based immunotherapy and is associated with a reduction in the numbers and suppressive function of MDSC. These data suggest that immunotherapy approaches benefit from simultaneously blocking cyclooxygenase-2 activity

  13. Immunotherapy of elderly acute myeloid leukemia: light at the end of a long tunnel?

    Science.gov (United States)

    Rafelson, William M; Reagan, John L; Fast, Loren D; Lim, Seah H

    2017-11-01

    Although it is possible to induce remission in the majority of the patients with acute myeloid leukemia (AML), many patients still die due to disease relapse. Immunotherapy is an attractive option. It is more specific. The memory T cells induced by immunotherapy may also provide the long-term tumor immunosurveillance to prevent disease relapse. Although immunotherapy of AML started in the early 1970s, its clinical impact has been disappointing. Recent advances in tumor immunology and immunotherapeutic agents have rekindled interest. Here, we provide a review of the history of AML immunotherapy, discuss why AML is well suited for immunotherapeutic approaches and present the biological obstacles that affect the success of immunotherapy. Finally, we put forward a new paradigm of AML immunotherapy that utilizes a combination of immunotherapeutic agents sequentially to enhance the in vivo tumor immunogenicity and effective priming and propagation of tumor-specific cytotoxic T cells.

  14. MRI in Glioma Immunotherapy: Evidence, Pitfalls, and Perspectives

    Directory of Open Access Journals (Sweden)

    Domenico Aquino

    2017-01-01

    Full Text Available Pseudophenomena, that is, imaging alterations due to therapy rather than tumor evolution, have an important impact on the management of glioma patients and the results of clinical trials. RANO (response assessment in neurooncology criteria, including conventional MRI (cMRI, addressed the issues of pseudoprogression after radiotherapy and concomitant chemotherapy and pseudoresponse during antiangiogenic therapy of glioblastomas (GBM and other gliomas. The development of cancer immunotherapy forced the identification of further relevant response criteria, summarized by the iRANO working group in 2015. In spite of this, the unequivocal definition of glioma progression by cMRI remains difficult particularly in the setting of immunotherapy approaches provided by checkpoint inhibitors and dendritic cells. Advanced MRI (aMRI may in principle address this unmet clinical need. Here, we discuss the potential contribution of different aMRI techniques and their indications and pitfalls in relation to biological and imaging features of glioma and immune system interactions.

  15. Mutanome Engineered RNA Immunotherapy: Towards Patient-Centered Tumor Vaccination

    Directory of Open Access Journals (Sweden)

    Mathias Vormehr

    2015-01-01

    Full Text Available Advances in nucleic acid sequencing technologies have revolutionized the field of genomics, allowing the efficient targeting of mutated neoantigens for personalized cancer vaccination. Due to their absence during negative selection of T cells and their lack of expression in healthy tissue, tumor mutations are considered as optimal targets for cancer immunotherapy. Preclinical and early clinical data suggest that synthetic mRNA can serve as potent drug format allowing the cost efficient production of highly efficient vaccines in a timely manner. In this review, we describe a process, which integrates next generation sequencing based cancer mutanome mapping, in silico target selection and prioritization approaches, and mRNA vaccine manufacturing and delivery into a process we refer to as MERIT (mutanome engineered RNA immunotherapy.

  16. Novel Anti-Melanoma Immunotherapies: Disarming Tumor Escape Mechanisms

    Directory of Open Access Journals (Sweden)

    Sivan Sapoznik

    2012-01-01

    Full Text Available The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies. We describe new immunomodulatory approaches currently in the development pipeline, focus on the novel CEACAM1 immune checkpoint, and compare its potential to the extensively described targets, CTLA4 and PD1. This paper combines multi-disciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles.

  17. Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases.

    Science.gov (United States)

    Tran, Thanh-Huyen; Mattheolabakis, George; Aldawsari, Hibah; Amiji, Mansoor

    2015-09-01

    Cell secreted exosomes (30-100nm vesicles) play a major role in intercellular communication due to their ability to transfer proteins and nucleic acids from one cell to another. Depending on the originating cell type and the cargo, exosomes can have immunosuppressive or immunostimulatory effects, which have potential application as immunotherapies for cancer and autoimmune diseases. Cellular components shed from tumor cells or antigen presenting cells (APCs), such as dendritic cells, macrophages and B cells, have been shown to be efficiently packaged in exosomes. In this review, we focus on the application of exosomes as nanocarriers and immunological agents for cancer and autoimmune immunotherapy. APC-derived exosomes demonstrate effective therapeutic efficacy for the treatment of cancer and experimental autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition to their intrinsic immunomodulating activity, exosomes have many advantages over conventional nanocarriers for drug and gene delivery. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Targeting CD8+ T-cell tolerance for cancer immunotherapy.

    Science.gov (United States)

    Jackson, Stephanie R; Yuan, Jinyun; Teague, Ryan M

    2014-01-01

    In the final issue of Science in 2013, the American Association of Science recognized progress in the field of cancer immunotherapy as the 'Breakthrough of the Year.' The achievements were actually twofold, owing to the early success of genetically engineered chimeric antigen receptors (CAR) and to the mounting clinical triumphs achieved with checkpoint blockade antibodies. While fundamentally very different, the common thread of these independent strategies is the ability to prevent or overcome mechanisms of CD8(+) T-cell tolerance for improved tumor immunity. Here we discuss how circumventing T-cell tolerance has provided experimental insights that have guided the field of clinical cancer immunotherapy to a place where real breakthroughs can finally be claimed.

  19. DNA-inorganic hybrid nanovaccine for cancer immunotherapy

    Science.gov (United States)

    Zhu, Guizhi; Liu, Yijing; Yang, Xiangyu; Kim, Young-Hwa; Zhang, Huimin; Jia, Rui; Liao, Hsien-Shun; Jin, Albert; Lin, Jing; Aronova, Maria; Leapman, Richard; Nie, Zhihong; Niu, Gang; Chen, Xiaoyuan

    2016-03-01

    Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit cancer development. Unmethylated CpG dinucleotide-containing oligonucleotides (CpG), a class of potent adjuvants that activate the toll-like receptor 9 (TLR9) located in the endolysosome of many antigen-presenting cells (APCs), are promising for cancer immunotherapy. However, clinical application of synthetic CpG confronts many challenges such as suboptimal delivery into APCs, unfavorable pharmacokinetics caused by limited biostability and short in vivo half-life, and side effects associated with leaking of CpG into the systemic circulation. Here we present DNA-inorganic hybrid nanovaccines (hNVs) for efficient uptake into APCs, prolonged tumor retention, and potent immunostimulation and cancer immunotherapy. hNVs were self-assembled from concatemer CpG analogs and magnesium pyrophosphate (Mg2PPi). Mg2PPi renders hNVs resistant to nuclease degradation and thermal denaturation, both of which are demanding characteristics for effective vaccination and the storage and transportation of vaccines. Fluorophore-labeled hNVs were tracked to be efficiently internalized into the endolysosomes of APCs, where Mg2PPi was dissolved in an acidic environment and thus CpG analogs were exposed to hNVs. Internalized hNVs in APCs led to (1) elevated secretion of proinflammatory factors, and (2) elevated expression of co-stimulatory factors. Compared with molecular CpG, hNVs dramatically prolonged the tissue retention of CpG analogs and reduced splenomegaly, a common side effect of CpG. In a melanoma mouse model, two injections of hNVs significantly inhibited the tumor growth and outperformed the molecular CpG. These results suggest hNVs are promising for cancer immunotherapy.Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit

  20. Novel targets for natural killer/T-cell lymphoma immunotherapy.

    Science.gov (United States)

    Kumai, Takumi; Kobayashi, Hiroya; Harabuchi, Yasuaki

    2016-01-01

    Extranodal natural killer/T-cell lymphoma, nasal type (NKTL) is a rare but highly aggressive Epstein-Barr virus-related malignancy, which mainly occurs in nasopharyngeal and nasal/paranasal areas. In addition to its high prevalence in Asian, Central American and South American populations, its incidence rate has been gradually increasing in Western countries. The current mainstay of treatment is a combination of multiple chemotherapies and irradiation. Although chemoradiotherapy can cure NKTL, it often causes severe and fatal adverse events. Because a growing body of evidence suggests that immunotherapy is effective against hematological malignancies, this treatment could provide an alternative to chemoradiotherapy for treatment of NKTL. In this review, we focus on how recent findings could be used to develop efficient immunotherapies against NKTL.

  1. Current advances in T-cell-based cancer immunotherapy

    Science.gov (United States)

    Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

    2015-01-01

    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

  2. Advances of Immune Checkpoint Inhibitors in Tumor Immunotherapy

    Science.gov (United States)

    Guo, Qiao

    2018-01-01

    Immune checkpoints are cell surface molecules that can fine-tune the immune responses, they are crucial for modulating the duration and amplitude of immune reactions while maintaining self-tolerance in order to minimize autoimmune responses. Numerous studies have demonstrated that tumors cells can directly express immune-checkpoint molecules, or induce many inhibitory molecules expression in the tumor microenvironment to inhibit the anti-tumor immunity. Releasing these brakes has emerged as an exciting strategy to cure cancer. In the past few years, clinical trials with therapeutic antibodies targeting to the checkpoint molecules CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. In contrast to the conventional treatment, checkpoint inhibitors induce broad and durable antitumor responses. In the future, treatment may involve combination therapy to target different checkpoint molecules and stages of the adaptive immune responses. In this review, we summarized the recent advances of the study and development of other checkpoint molecules in tumor immunotherapy.

  3. Cytomegalovirus-targeted immunotherapy and glioblastoma: hype or hope?

    Science.gov (United States)

    Ferguson, Sherise D; Srinivasan, Visish M; Ghali, Michael Gz; Heimberger, Amy B

    2016-01-01

    Malignant gliomas, including glioblastoma (GBM), are the most common primary brain tumors. Despite extensive research only modest gains have been made in long-term survival. Standard of care involves maximizing safe surgical resection followed by concurrent chemoradiation with temozolomide. Immunotherapy for GBM is an area of intense research in recent years. New immunotherapies, although promising, have not been integrated into standard practice. Human cytomegalovirus (HCMV) is a DNA virus of the family Herpesviridae. Human seroprevalence is approximately 80%, and in most cases, is associated with asymptomatic infection. HCMV may be an important agent in the initiation, promotion and/or progression of tumorigenesis. Regardless of a possible etiologic role in GBM, interest has centered on exploiting this association for development of immunomodulatory therapies.

  4. Immuno senescence: implications for cancer immunotherapy in elderly patients

    International Nuclear Information System (INIS)

    Garcia, Beatriz; Lage, Agustin

    2006-01-01

    The aging process produces functional and developmental changes in the immune system. Those changes may occur at different levels or at different moments, from lymphopoiesis up to the final response of the immune system facing a certain disease. The response of the adaptive immune system is most strongly affected by the aging process, particularly at the level of the effector T-cells. These changes can have a negative impact on the immune response of elderly patients during cancer immunotherapy. The present paper is an updated review of the bibliography on the most important modifications produced in the immune system during aging, as well as on the relevance of these modifications for the design of new strategies for cancer immunotherapy. (Author)

  5. The interplay of immunotherapy and chemotherapy: harnessing potential synergies.

    Science.gov (United States)

    Emens, Leisha A; Middleton, Gary

    2015-05-01

    Although cancer chemotherapy has historically been considered immune suppressive, it is now accepted that certain chemotherapies can augment tumor immunity. The recent success of immune checkpoint inhibitors has renewed interest in immunotherapies, and in combining them with chemotherapy to achieve additive or synergistic clinical activity. Two major ways that chemotherapy promotes tumor immunity are by inducing immunogenic cell death as part of its intended therapeutic effect and by disrupting strategies that tumors use to evade immune recognition. This second strategy, in particular, is dependent on the drug, its dose, and the schedule of chemotherapy administration in relation to antigen exposure or release. In this Cancer Immunology at the Crossroads article, we focus on cancer vaccines and immune checkpoint blockade as a forum for reviewing preclinical and clinical data demonstrating the interplay between immunotherapy and chemotherapy. ©2015 American Association for Cancer Research.

  6. Immunotherapy in Merkel cell carcinoma: role of Avelumab

    Directory of Open Access Journals (Sweden)

    Palla AR

    2018-03-01

    Full Text Available Amruth R Palla, Donald Doll Department of Internal Medicine, Division of Hematology and Oncology, Ellis Fischel Cancer Center, University of Missouri, Columbia, MO, USA Abstract: Merkel cell carcinoma (MCC, a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer. Keywords: Merkel cell carcinoma, T cell, PD-L1, Avelumab, immunotherapy, check point inhibitors, neuroendocrine tumor

  7. Lymphoma immunotherapy: vaccines, adoptive cell transfer and immunotransplant

    Science.gov (United States)

    Brody, Joshua; Levy, Ronald

    2017-01-01

    Therapy for non-Hodgkin lymphoma has benefited greatly from basic science and clinical research such that chemotherapy and monoclonal antibody therapy have changed some lymphoma subtypes from uniformly lethal to curable, but the majority of lymphoma patients remain incurable. Novel therapies with less toxicity and more specific targeting of tumor cells are needed and immunotherapy is among the most promising of these. Recently completed randomized trials of idiotype vaccines and earlier-phase trials of other vaccine types have shown the ability to induce antitumor T cells and some clinical responses. More recently, trials of adoptive transfer of antitumor T cells have demonstrated techniques to increase the persistence and antitumor effect of these cells. Herein, we discuss lymphoma immunotherapy clinical trial results and what lessons can be taken to improve their effect, including the combination of vaccination and adoptive transfer in an approach we have dubbed ‘immunotransplant’. PMID:20636025

  8. Cancer immunotherapy: Breakthrough or "deja vu, all over again"?

    Science.gov (United States)

    Sell, Stewart

    2017-06-01

    From the application of Coley's toxin in the early 1900s to the present clinical trials using immune checkpoint regulatory inhibitors, the history of cancer immunotherapy has consisted of extremely high levels of enthusiasm after anecdotal case reports of enormous success, followed by decreasing levels of enthusiasm as the results of controlled clinical trials are available. In this review, this pattern will be documented for the various immunotherapeutic approaches over the years. The sole exception being vaccination against cancer causing viruses, which have already prevented thousands of cancers. We can only hope that the present high level of enthusiasm for the use of immune stimulation by removal of blocks to cancer immunity will be more productive than the incremental improvements using previous immunotherapies.

  9. Radio-immunotherapy of non Hodgkin lymphomas: Experience from Lille

    International Nuclear Information System (INIS)

    Huglo, D.; Morschhauser, F.; Steinling, M.; Huglo, D.; Prangere, T.; Robu, D.; Malek, E.; Petyt, G.; Steinling, M.; Huglo, D.; Morschhauser, F.; Robu, D.

    2009-01-01

    From an experience of radio-immunotherapy of non Hodgkin lymphomas from March 2002 to December 2008 (near 7 years), corresponding to 160 treatments, an analysis of indications has been done: clinical research trials, authorized indications from A.M.M. or medically justified. Some elements which could be problematic are pointed: coordination between the regional Haematology departments and our Nuclear Medicine department, radio labelling and radioprotection. (authors)

  10. The next generation of immunotherapy: keeping lung cancer in check

    Directory of Open Access Journals (Sweden)

    Ashwin Somasundaram

    2017-04-01

    Full Text Available Abstract Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy. Therefore, PD-1 inhibitors such as nivolumab and pembrolizumab were rapidly approved for both squamous and nonsquamous lung cancer in the pretreated population. The advent of these new therapies have revolutionized the treatment of lung cancer; however, the majority of NSCLC patients still do not respond to PD-1/PD-L1 inhibition leaving an unmet need for a large and growing population. Immunotherapy combinations with chemotherapy, radiation therapy, or novel immunomodulatory agents are currently being examined with the hope of achieving higher response rates and improving overall survival rate. Chemotherapy and radiation therapy has been theorized to increase the release of tumor antigen leading to increased responses with immunotherapy. However, cytotoxic chemotherapy and radiation therapy may also destroy actively proliferating T cells. The correct combination and order of therapy is under investigation. The majority of patients who do respond to immunotherapy have a durable response attributed to the effect of adaptive immune system’s memory. Unfortunately, some patients’ tumors do progress afterward and investigation of checkpoint blockade resistance is still nascent. This review will summarize the latest efficacy and safety data for early and advanced NSCLC in both the treatment-naïve and

  11. CDK5-A Novel Role in Prostate Cancer Immunotherapy

    Science.gov (United States)

    2017-10-01

    castration resistant prostate cancer (CRPC) Specific Aims: 1. Effect of dinaciclib on androgen receptor (AR) S81 phosphorylation and function. 2. Effect of...circulating tumor DNA (ctDNA) and T-cell receptor (TCR) repertoire profiling as biomarkers for men with oligometastatic prostate cancer treated with...AWARD NUMBER: W81XWH-15-1-0670 TITLE: CDK5-A Novel Role in Prostate Cancer Immunotherapy PRINCIPAL INVESTIGATOR: Dr. Barry Nelkin

  12. Is immunotherapy an opportunity for effective treatment of drug addiction?

    Science.gov (United States)

    Zalewska-Kaszubska, Jadwiga

    2015-11-27

    Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Reconceptualizing cancer immunotherapy based on plant production systems

    OpenAIRE

    Hefferon, Kathleen

    2017-01-01

    Plants can be used as inexpensive and facile production platforms for vaccines and other biopharmaceuticals. More recently, plant-based biologics have expanded to include cancer immunotherapy agents. The following review describes the current state of the art for plant-derived strategies to prevent or reduce cancers. The review discusses avenues taken to prevent infection by oncogenic viruses, solid tumors and lymphomas. Strategies including cancer vaccines, monoclonal antibodies and virus na...

  14. Basis for molecular diagnostics and immunotherapy for esophageal cancer.

    Science.gov (United States)

    Abdo, Joe; Agrawal, Devendra K; Mittal, Sumeet K

    2017-01-01

    Esophageal cancer (EC) is an extremely aggressive neoplasm, diagnosed in about 17,000 Americans every year with a mortality rate of more than 80% within five years and a median overall survival of just 13 months. For decades, the go-to regimen for esophageal cancer patients has been the use of taxane and platinum-based chemotherapy regimens, which has yielded the field's most dire survival statistics. Areas covered: Combination immunotherapy and a more robust molecular diagnostic platform for esophageal tumors could improve patient management strategies and potentially extend lives beyond the current survival figures. Analyzing a panel of biomarkers including those affiliated with taxane and platinum resistance (ERCC1 and TUBB3) as well as immunotherapy effectiveness (PD-L1) would provide oncologists more information on how to optimize first-line therapy for EC. Expert commentary: Of the 12 FDA-approved therapies in EC, zero target the genome. A majority of the approved drugs either target or are effected by proteomic expression. Therefore, a broader understanding of diagnostic biomarkers could give more clarity and direction in treating esophageal cancer in concert with a greater use of immunotherapy.

  15. Immunotherapy with neuraminidase-treated tumor cells after radiotherapy

    International Nuclear Information System (INIS)

    Song, C.W.; Levitt, S.H.

    1975-01-01

    The effect of active immunotherapy with Vibrio cholerae neuraminidase-treated syngeneic tumor cells (VCN-cells) following radiotherapy has been studied with 3-methylcholanthrene-induced fibrosarcoma, M-79, transplanted to the thigh of C3H/HeJ mice. When the tumors reached 4 to 8 mm in diameter, various treatments were started. X-irradiation with 2000 rad in a single dose induced a complete regression of 24 out of 103 tumors (23.3 percent). The inoculation of 1 x 10 6 of VCN-cells to the tumor-bearing animals, every other day for a total of three doses, caused a complete regression of 6 out of 57 tumors (10.5 percent). Treatments of animals with the immunotherapy starting 1 day after X-irradiation of tumors with 2000 rad resulted in a complete regression of 22 out of 58 tumors (37.9 percent). The median survival time of animals that received combined radiotherapy and immunotherapy was longer than that observed after either treatment alone

  16. Novel immunotherapy approaches for metastatic urothelial and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhiying Shao

    2016-10-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC and urothelial carcinoma (UC remains a major challenge. Past research has implicated the immune system in tumor surveillance of both malignancies, leading to the application of immunotherapy agents for both cancers. Among them, the most promising agents are the checkpoint blockade drugs, such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, programmed death receptor 1 (PD-1, and PD-1 ligand (PD-L1. In normal physiology, these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions, which is pivotal for maintaining self-tolerance. However, tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response, leading to disease progression and metastasis. Thus, there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC. To date, nivolumab (anti-PD-1 and atezolizumab (anti-PD-L1 have been approved for the treatment of metastatic RCC and UC, respectively. Despite these successes, challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach. In this report, we review existing data and research on immunotherapy in metastatic RCC and UC.

  17. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    International Nuclear Information System (INIS)

    Weir, Genevieve M.; Liwski, Robert S.; Mansour, Marc

    2011-01-01

    Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments

  18. Patient Susceptibility to Candidiasis—A Potential for Adjunctive Immunotherapy

    Science.gov (United States)

    Davidson, Linda; Netea, Mihai G.; Kullberg, Bart Jan

    2018-01-01

    Candida spp. are colonizing fungi of human skin and mucosae of the gastrointestinal and genitourinary tract, present in 30–50% of healthy individuals in a population at any given moment. The host defense mechanisms prevent this commensal fungus from invading and causing disease. Loss of skin or mucosal barrier function, microbiome imbalances, or defects of immune defense mechanisms can lead to an increased susceptibility to severe mucocutaneous or invasive candidiasis. A comprehensive understanding of the immune defense against Candida is essential for developing adjunctive immunotherapy. The important role of underlying genetic susceptibility to Candida infections has become apparent over the years. In most patients, the cause of increased susceptibility to fungal infections is complex, based on a combination of immune regulation gene polymorphisms together with other non-genetic predisposing factors. Identification of patients with an underlying genetic predisposition could help determine which patients could benefit from prophylactic antifungal treatment or adjunctive immunotherapy. This review will provide an overview of patient susceptibility to mucocutaneous and invasive candidiasis and the potential for adjunctive immunotherapy. PMID:29371502

  19. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

    2011-08-05

    Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  20. Mathematical Model Creation for Cancer Chemo-Immunotherapy

    Directory of Open Access Journals (Sweden)

    Lisette de Pillis

    2009-01-01

    Full Text Available One of the most challenging tasks in constructing a mathematical model of cancer treatment is the calculation of biological parameters from empirical data. This task becomes increasingly difficult if a model involves several cell populations and treatment modalities. A sophisticated model constructed by de Pillis et al., Mixed immunotherapy and chemotherapy of tumours: Modelling, applications and biological interpretations, J. Theor. Biol. 238 (2006, pp. 841–862; involves tumour cells, specific and non-specific immune cells (natural killer (NK cells, CD8+T cells and other lymphocytes and employs chemotherapy and two types of immunotherapy (IL-2 supplementation and CD8+T-cell infusion as treatment modalities. Despite the overall success of the aforementioned model, the problem of illustrating the effects of IL-2 on a growing tumour remains open. In this paper, we update the model of de Pillis et al. and then carefully identify appropriate values for the parameters of the new model according to recent empirical data. We determine new NK and tumour antigen-activated CD8+T-cell count equilibrium values; we complete IL-2 dynamics; and we modify the model in de Pillis et al. to allow for endogenous IL-2 production, IL-2-stimulated NK cell proliferation and IL-2-dependent CD8+T-cell self-regulations. Finally, we show that the potential patient-specific efficacy of immunotherapy may be dependent on experimentally determinable parameters.

  1. Patient Susceptibility to Candidiasis—A Potential for Adjunctive Immunotherapy

    Directory of Open Access Journals (Sweden)

    Linda Davidson

    2018-01-01

    Full Text Available Candida spp. are colonizing fungi of human skin and mucosae of the gastrointestinal and genitourinary tract, present in 30–50% of healthy individuals in a population at any given moment. The host defense mechanisms prevent this commensal fungus from invading and causing disease. Loss of skin or mucosal barrier function, microbiome imbalances, or defects of immune defense mechanisms can lead to an increased susceptibility to severe mucocutaneous or invasive candidiasis. A comprehensive understanding of the immune defense against Candida is essential for developing adjunctive immunotherapy. The important role of underlying genetic susceptibility to Candida infections has become apparent over the years. In most patients, the cause of increased susceptibility to fungal infections is complex, based on a combination of immune regulation gene polymorphisms together with other non-genetic predisposing factors. Identification of patients with an underlying genetic predisposition could help determine which patients could benefit from prophylactic antifungal treatment or adjunctive immunotherapy. This review will provide an overview of patient susceptibility to mucocutaneous and invasive candidiasis and the potential for adjunctive immunotherapy.

  2. Immunological Changes on Allergic Response after Beevenom Immunotherapy

    Directory of Open Access Journals (Sweden)

    Dong-Ha Han

    2004-12-01

    Full Text Available Beevenom immunotherapy(BVIT in allergic patients is a well-established treatment modality for the prevention of systemic anaphylactic reactions caused by insect stings. BVIT is accompanied by increases in allergen-specific IgG, particularly the IgG4 isotype, which blocks not only IgE-dependent histamine release from basophils but also IgE-mediated antigen presentation to T cells. Inhibition of T cells after BVIT also involves decreased induction of the costimulatory molecule ICOS, which, in turn, seems to be dependent on the presence of IL-10, also associated with the inhibited status of T cells after BVIT. Suppression of T cells by IL-10 is an active process, which depends on the expression and participation of CD28. Immune tolerance in specific allergen immunotherapy might be a consequence of decreased Th2 or increased Th1 response of allergen specific T lymphocytes. BVIT shifted cytokine responses to allergen from a TH-2 to a TH-1 dominant pattern, suggesting direct effects on T cells. Many studies showed that severe side effects due to venom immunotherapy are rare. These results suggest that immunological changes after BVIT may be applied to be therapeutic alternative of general allergic diseases including beevenom allergy.

  3. Debut of Gastroesophageal Reflux Concomitant with Administration of Sublingual Immunotherapy

    Directory of Open Access Journals (Sweden)

    Jacob Juel

    2017-01-01

    Full Text Available Gastroesophageal reflux disease (GORD is an often debilitating condition characterised by retrograde flow of content from stomach into the oesophagus, where the low pH of the stomach acid irritates the mucosa of the oesophagus. The most dominant symptoms in GORD are pyrosis, regurgitation, and dysphagia. Sublingual immunotherapy (SLIT was first described in 1986. Following this description, the use has greatly increased in the treatment of allergic rhinitis, as an alternative to subcutaneously administered immunotherapy. Side effects are commonly of oropharyngeal and gastrointestinal nature, for example, swelling, itching, irritation, ulceration of the oropharynx and nausea, abdominal pain, vomiting, and diarrhoea. More serious side effects are dominated by respiratory tract and systemic manifestations. A 30-year-old male experienced refractory, relentless, and debilitation GORD subsequent to administration of sublingual immunotherapy for house dust mite in allergic rhinitis. The patient had to stop the SLIT after two weeks of administration due to GORD. The cessation resulted in rapid resolution of symptoms.

  4. Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study

    Science.gov (United States)

    Jung, Keun-Hwa; Sunwoo, Jun-Sang; Moon, Jangsup; Lim, Jung-Ah; Lee, Doo Young; Shin, Yong-Won; Kim, Tae-Joon; Lee, Keon-Joo; Lee, Woo-Jin; Lee, Han-Sang; Jun, Jinsun; Kim, Dong-Yub; Kim, Man-Young; Kim, Hyunjin; Kim, Hyeon Jin; Suh, Hong Il; Lee, Yoojin; Kim, Dong Wook; Jeong, Jin Ho; Choi, Woo Chan; Bae, Dae Woong; Shin, Jung-Won; Jeon, Daejong; Park, Kyung-Il; Jung, Ki-Young; Chu, Kon; Lee, Sang Kun

    2016-01-01

    Objective To evaluate the seizure characteristics and outcome after immunotherapy in adult patients with autoimmune encephalitis (AE) and new-onset seizure. Methods Adult (age ≥18 years) patients with AE and new-onset seizure who underwent immunotherapy and were followed-up for at least 6 months were included. Seizure frequency was evaluated at 2–4 weeks and 6 months after the onset of the initial immunotherapy and was categorized as “seizure remission”, “> 50% seizure reduction”, or “no change” based on the degree of its decrease. Results Forty-one AE patients who presented with new-onset seizure were analysed. At 2–4 weeks after the initial immunotherapy, 51.2% of the patients were seizure free, and 24.4% had significant seizure reduction. At 6 months, seizure remission was observed in 73.2% of the patients, although four patients died during hospitalization. Rituximab was used as a second-line immunotherapy in 12 patients who continued to have seizures despite the initial immunotherapy, and additional seizure remission was achieved in 66.6% of them. In particular, those who exhibited partial response to the initial immunotherapy had a better seizure outcome after rituximab, with low adverse events. Conclusion AE frequently presented as seizure, but only 18.9% of the living patients suffered from seizure at 6 months after immunotherapy. Aggressive immunotherapy can improve seizure outcome in patients with AE. PMID:26771547

  5. Non-infectious cholecystopathy secondary to high-dose IL-2 cancer immunotherapy

    International Nuclear Information System (INIS)

    Kuppler, Kevin; Jeong, Daniel; Choi, Jung W

    2015-01-01

    Interleukin-2 (IL-2) associated cholecystopathy is a rare manifestation of IL-2 drug toxicity in the setting of cancer immunotherapy. While the imaging data and clinical presentation can easily mimic acute cholecystitis, the correct diagnosis can be made with the particular clinical history, thus avoiding inappropriate surgical management. As more cancer immunotherapies become standard oncologic treatments, specific immunotherapy-associated side effects are also expected to be encountered more frequently in the future and should be recognized as such. We present a case of IL-2-associated cholecystopathy in the setting of renal cell carcinoma immunotherapy

  6. Dendritic Cell-Based Immunotherapy of Breast Cancer: Modulation by CpG

    National Research Council Canada - National Science Library

    Baar, Joseph

    2004-01-01

    ... in the United States in 2004. Thus, patients with MBC who fail conventional therapies are candidates for clinical trials using novel therapeutic approaches, including immunotherapy. Dendritic cells (DC...

  7. Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study.

    Directory of Open Access Journals (Sweden)

    Jung-Ick Byun

    Full Text Available To evaluate the seizure characteristics and outcome after immunotherapy in adult patients with autoimmune encephalitis (AE and new-onset seizure.Adult (age ≥18 years patients with AE and new-onset seizure who underwent immunotherapy and were followed-up for at least 6 months were included. Seizure frequency was evaluated at 2-4 weeks and 6 months after the onset of the initial immunotherapy and was categorized as "seizure remission", "> 50% seizure reduction", or "no change" based on the degree of its decrease.Forty-one AE patients who presented with new-onset seizure were analysed. At 2-4 weeks after the initial immunotherapy, 51.2% of the patients were seizure free, and 24.4% had significant seizure reduction. At 6 months, seizure remission was observed in 73.2% of the patients, although four patients died during hospitalization. Rituximab was used as a second-line immunotherapy in 12 patients who continued to have seizures despite the initial immunotherapy, and additional seizure remission was achieved in 66.6% of them. In particular, those who exhibited partial response to the initial immunotherapy had a better seizure outcome after rituximab, with low adverse events.AE frequently presented as seizure, but only 18.9% of the living patients suffered from seizure at 6 months after immunotherapy. Aggressive immunotherapy can improve seizure outcome in patients with AE.

  8. Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy.

    Science.gov (United States)

    Schubert, R; Eickmeier, O; Garn, H; Baer, P C; Mueller, T; Schulze, J; Rose, M A; Rosewich, M; Renz, H; Zielen, S

    2009-01-01

    Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy. A total of 34 children (6-18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgG(Mite) and IgG4(Mite), by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3. There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgG(Mite) (p classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups. Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients. (c) 2008 S. Karger AG, Basel.

  9. Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Antonio Aguilar-Pimentel

    Full Text Available Allergen-specific immunotherapy (AIT is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma.Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways.In C57BL/6J mice, a model of ovalbumin (OVA-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro.AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells.This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis.

  10. Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma.

    Science.gov (United States)

    Aguilar-Pimentel, Antonio; Graessel, Anke; Alessandrini, Francesca; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Russkamp, Dennis; Chaker, Adam; Ollert, Markus; Blank, Simon; Gutermuth, Jan; Schmidt-Weber, Carsten B

    2017-01-01

    Allergen-specific immunotherapy (AIT) is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma. Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways. In C57BL/6J mice, a model of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro. AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells. This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis.

  11. Spatially selective depleting tumor-associated negative regulatory T-(Treg) cells with near infrared photoimmunotherapy (NIR-PIT): A new cancer immunotherapy (Conference Presentation)

    Science.gov (United States)

    Kobayashi, Hisataka

    2017-02-01

    Near infrared photoimmunotherapy (NIR-PIT) is a new type of molecularly-targeted photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IR700, to a monoclonal antibody (MAb) targeting target-specific cell-surface molecules. When exposed to NIR light, the conjugate rapidly induces a highly-selective cell death only in receptor-positive, MAb-IR700-bound cells. Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting anti-tumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4+CD25+Foxp3+ regulatory T cells (Tregs) are well-known immune-suppressor cells that play a key role in tumor immuno-evasion and have been the target of systemic immunotherapies. We used CD25-targeted NIR-PIT to selectively deplete Tregs, thus activating CD8+ T and NK cells and restoring local anti-tumor immunity. This not only resulted in regression of the treated tumor but also induced responses in separate untreated tumors of the same cell-line derivation. We conclude that CD25-targeted NIR-PIT causes spatially selective depletion of Tregs, thereby providing an alternative approach to cancer immunotherapy that can treat not only local tumors but also distant metastatic tumors.

  12. Desmoplastic Tumor Microenvironment and Immunotherapy in Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Høgdall, Dan; Lewinska, Monika; Andersen, Jesper B

    2018-01-01

    connective tissue which surrounds and infiltrates the tumor epithelium. This desmoplastic environment presents a clinical challenge, limiting drug delivery and supporting the growth of the tumor mass. In this review we attempt to highlight key pathways involved in cell to cell communication between the tumor......Cholangiocarcinoma (CCA) is a dismal disease which often is diagnosed at a late stage where the tumor is locally advanced, metastatic, and, as a result, is associated with low resectability. The heterogeneity of this cancer type is a major reason why the majority of patients fail to respond...... to therapy, and surgery remains their only curative option. Among patients who undergo surgical intervention, such tumors typically recur in 50% of cases within 1year. Thus, CCA is among the most aggressive and chemoresistant malignancies. CCA is characterized by marked tumor reactive stroma, a fibrogenic...

  13. Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies.

    Science.gov (United States)

    Monjazeb, Arta M; Kent, Michael S; Grossenbacher, Steven K; Mall, Christine; Zamora, Anthony E; Mirsoian, Annie; Chen, Mingyi; Kol, Amir; Shiao, Stephen L; Reddy, Abhinav; Perks, Julian R; T N Culp, William; Sparger, Ellen E; Canter, Robert J; Sckisel, Gail D; Murphy, William J

    2016-09-01

    Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects. These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model

    NARCIS (Netherlands)

    Vissers, Joost L. M.; van Esch, Betty C. A. M.; Hofman, Gerard A.; Kapsenberg, Martien L.; Weller, Frank R.; van Oosterhout, Antoon J. M.

    2004-01-01

    Background: Human studies have demonstrated that allergen immunotherapy induces memory suppressive responses and IL-10 production by allergen-specific T cells. Previously, we established a mouse model in which allergen immunotherapy was effective in the suppression of allergen-induced asthma

  15. Checkpoint inhibitors in advanced melanoma: effect on the field of immunotherapy.

    Science.gov (United States)

    O'reilly, Aine; Larkin, James

    2017-07-01

    The success of the immune checkpoint inhibitors in melanoma has reinvigorated the field of immunotherapy. Immune checkpoint inhibitors are now the standard of care in multiple cancer types including lung cancer, head and neck cancer, urothelial cancer and renal cell cancer. The field of immunotherapy is currently expanding rapidly and will be a focus of research and development for decades to come. Areas covered: This review covers the early development of immune checkpoint inhibitors and the changes that occurred in the drug development paradigm to facilitate the development of immunotherapy. The review will summarise the areas into which immune checkpoint inhibitors have been adopted and will review the data that supported this. Furthermore, we will discuss future developments in immunotherapy and the current landscape regarding maximising the potential of immunotherapy in clinical practice. Expert commentary: In the author's opinion, the potential of immunotherapy is vast. To date immune checkpoint inhibition has already delivered durable responses in a proportion of patients with cancer types which were previously universally lethal. The future of immunotherapy will rely upon the intelligent application of translational research to clinical practice, such that immunotherapy can be effective for a wider population and maintain its current growth.

  16. Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape.

    Science.gov (United States)

    Emens, Leisha A; Ascierto, Paolo A; Darcy, Phillip K; Demaria, Sandra; Eggermont, Alexander M M; Redmond, William L; Seliger, Barbara; Marincola, Francesco M

    2017-08-01

    Cancer immunotherapy is now established as a powerful way to treat cancer. The recent clinical success of immune checkpoint blockade (antagonists of CTLA-4, PD-1 and PD-L1) highlights both the universal power of treating the immune system across tumour types and the unique features of cancer immunotherapy. Immune-related adverse events, atypical clinical response patterns, durable responses, and clear overall survival benefit distinguish cancer immunotherapy from cytotoxic cancer therapy. Combination immunotherapies that transform non-responders to responders are under rapid development. Current challenges facing the field include incorporating immunotherapy into adjuvant and neoadjuvant cancer therapy, refining dose, schedule and duration of treatment and developing novel surrogate endpoints that accurately capture overall survival benefit early in treatment. As the field rapidly evolves, we must prioritise the development of biomarkers to guide the use of immunotherapies in the most appropriate patients. Immunotherapy is already transforming cancer from a death sentence to a chronic disease for some patients. By making smart, evidence-based decisions in developing next generation immunotherapies, cancer should become an imminently treatable, curable and even preventable disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Immunotherapy in children and adolescents with allergic rhinoconjunctivitis : a systematic review

    NARCIS (Netherlands)

    Roeder, Esther; Berger, Marjolein Y.; de Groot, Hans; van Wijk, Roy Gerth

    Allergen-specific immunotherapy is one of the cornerstones of allergic rhinoconjunctivitis treatment. Since the development of non-invasive administration forms with better safety profiles, there is an increasing tendency to prescribe immunotherapy in youngsters. However, no overview is available on

  18. Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy

    DEFF Research Database (Denmark)

    da Cunha-Bang, C; Simonsen, J; Rostgaard, K

    2016-01-01

    The treatment of chronic lymphocytic leukemia (CLL) is in rapid transition, and during recent decades both combination chemotherapy and immunotherapy have been introduced. To evaluate the effects of this development, we identified all CLL patients registered in the nation-wide Danish Cancer...... for patients treated with chemo-immunotherapy demonstrated in clinical studies....

  19. The synergy between ionizing radiation and immunotherapy in the treatment of prostate cancer.

    Science.gov (United States)

    Sathianathen, Niranjan J; Krishna, Suprita; Konety, Badrinath R; Griffith, Thomas S

    2017-09-01

    There has been a surge in the use of immunotherapy for genitourinary malignancies. Immunotherapy is an established treatment for metastatic renal cell carcinoma and nonmuscle invasive bladder cancer, but its potential for treating prostate cancer (PCa) remains under investigation. Despite reported survival benefits, no published Phase III PCa trials using immunotherapy only as a treatment has demonstrated direct antitumor effects by reducing prostate-specific antigen levels. Subsequently, the thought of combining immunotherapy with other treatment modalities has gained traction as a way to achieving optimal results. Based on data from other malignancies, it is hypothesized that radiotherapy and immunotherapy can act synergistically to improve outcomes. We will discuss the clinical potential of combining immune-based treatments with radiotherapy as a treatment for advanced PCa.

  20. Combination therapy with radiation and OK-432 immunotherapy of cancer patients

    International Nuclear Information System (INIS)

    Hashimoto, Shozo; Miyamoto, Hiroshi

    1978-01-01

    We treated cancer patients with radiotherapy alone and with radiation plus immunotherapy at the Department of Radiology, Keio University Hospital. In all of the cancer patients who had radiationtherapy alone, a general depression in their immune reactivity was seen, but not seen in those who received radiationtherapy plus immunotherapy. Immunotherapy is defined as a stimulator of cancer patient's immune reaction. Usually radiationtherapy caused lymphopenia in which mainly T lymphocytes were decreased in number selectively, but there was no lymphopenia in cases treated with immunotherapy. We have performed nonspecific immunotherapy with OK-432. The result indicated that T lymphocytes were increased by OK-432 in spite of radiationtherapy. From this fact, OK-432 will be useful for suppression of metastasis and regression of tumors. (auth.)

  1. Combined effect of angioinfarction with immunotherapy in patients with stage IV renal cell carcinoma

    International Nuclear Information System (INIS)

    Oh, Joo Hyeong; Yoon, Yup; Jeong, Yu Mee; Ko, Young Tae; Chang, Sung Goo

    1994-01-01

    To assess the combined effectiveness of angioinfarction and immunotherapy for improving survival in patients with stage IV renal cell carcinoma. During the past 3 years, 13 patients of stage IV renal cell carcinoma were treated with angioinfarction and immunotherapy. Angioinfarction was performed on these 13 patients using absolute ethanol and occlusive balloon catheter. After angioinfarction, Interferon alpha was used for immunotherapy. For our analysis, 12 control patients of stage IV renal cell carcinoma without treatment were included in the study. Survival has been calculated according to the Kaplan and Meier method. The 1 year survival rate and median survival time in patients treated with angioinfarction and immunotherapy, were 46% and 13 months and in patients without treatment, 16% and 4 months, respectively. The combined treatment of angioinfarction and immunotherapy is of considerable value for improving survival in patients with stage IV renal cell carcinoma

  2. Plasma Onco-Immunotherapy: Novel Approach to Cancer Treatment

    Science.gov (United States)

    Fridman, Alexander

    2015-09-01

    Presentation is reviewing the newest results obtained by researchers of A.J. Drexel Plasma Institute on direct application of non-thermal plasma for direct treatment of different types of cancer by means of specific stimulation of immune system in the frameworks of the so-called onco-immunotherapy. Especial attention is paid to analysis of depth of penetration of different plasma-medical effects, from ROS, RNS, and ions to special biological signaling and immune system related processes. General aspects of the plasma-stimulation of immune system are discussed, pointing out specific medical applications. Most of experiments have been carried out using nanosecond pulsed DBD at low power and relatively low level of treatment doses, guaranteeing non-damage no-toxicity treatment regime. The nanosecond pulsed DBD physics is discussed mostly regarding its space uniformity and control of plasma parameters relevant to plasma medical treatment, and especially relevant to depth of penetration of different plasma medical effects. Detailed mechanism of the plasma-induced onco-immunotherapy has been suggested based upon preliminary in-vitro experiments with DBD treatment of different cancer cells. Sub-elements of this mechanism related to activation of macrophages and dendritic cells, specific stressing of cancer cells and the immunogenic cell death (ICD) are to be discussed based on results of corresponding in-vitro experiments. In-vivo experiments focused on the plasma-induced onco-immunotherapy were carried out in collaboration with medical doctors from Jefferson University hospital of Philadelphia. Todays achievements and nearest future prospective of clinical test focused on plasma-controlled cancer treatment are discussed in conclusion.

  3. Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.

    Science.gov (United States)

    Smith, Mark C; Zimmerman, M Bridget; Burke, Diane K; Bauman, Nancy M; Sato, Yutaka; Smith, Richard J H

    2009-01-01

    To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%). Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001). OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM. ClinicalTrials.gov Identifier: NCT00010452.

  4. Component-resolved diagnostics to direct in venom immunotherapy

    DEFF Research Database (Denmark)

    Blank, Simon; Bilò, Maria Beatrice; Ollert, Markus

    2018-01-01

    , the increasing knowledge about the molecular structure and relevance of important venom allergens and their availability as recombinant allergens, devoid of cross-reactive carbohydrate determinants, resulted in the development of an advanced component-resolved diagnostics (CRD) approach in venom allergy. Already...... immunotherapeutic intervention. Moreover, the detailed knowledge about sensitization profiles on a molecular level might open new options to identify patients who are at increased risk for side effects or not to respond to immunotherapy. Therefore, increasing potential of CRD becomes evident, to direct therapeutic...

  5. [Psychological aspects of immunotherapies in the treatment of malignant melanoma].

    Science.gov (United States)

    Kovács, Péter; Pánczél, Gitta; Melegh, Krisztina; Balatoni, Tímea; Pörneczy, Edit; Lõrincz, Lenke; Czirbesz, Kata; Gorka, Eszter; Liszkay, Gabriella

    2016-03-02

    Psychological problems may arise in connection with oncomedical treatments in three ways: 1. acute and/or 2. chronic ways, as well as 3. co-morbid psychiatric diseases that already exist must also be taken into account. Immunotherapies have the most common and also clinically relevant psychological side effects. Fatigue, anhedonia, social isolation, psychomotor slowness is reported during treatment. Anti-CTLA-4 antibody (ipilimumab) immunotherapy can present one of the most modern opportunities for adequate treatment for patients having distant metastasis or unresectable tumour. In relation to immunotherapies, acute psychological side effects (acute stress) emerging during treatments develop in a way that can mostly be linked to environmental factors, e.g. notification of diagnosis, hospitalisation, progression, deterioration in quality of life, imminent dates of control. Crisis is a temporary and threatening condition that endangers psychological balance. In such conditions, enhanced psychological vulnerability must be taken into account and doctors play a key role in the rapid recognition of the condition. Chronic psychological problems, which may arise from the depressogenic effect of the applied treatment or originated from a pre-melanoma psychiatric condition, may exceed the diagnostic and psychotherapeutic competences of a clinical psychologist. Even in case of a well-defined depressogenic biological mechanism such as the activation of the pro-inflammatory cytokine pathway, positive environmental effects can reduce symptoms and thus increase compliance. Side effects can be treated successfully using psychotherapeutic methods and/or psychiatric medicines. The application of routinely used complex psychosocial screening packages can provide the easiest method to identify worsening psychological condition during immunotherapy and give rapid feedback to the oncologist and the patient. Team work is of particular importance in a situation like this as it requires

  6. Immunotherapy in Merkel cell carcinoma: role of Avelumab.

    Science.gov (United States)

    Palla, Amruth R; Doll, Donald

    2018-01-01

    Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer.

  7. High hydrostatic pressure in cancer immunotherapy and biomedicine.

    Science.gov (United States)

    Adkins, Irena; Hradilova, Nada; Palata, Ondrej; Sadilkova, Lenka; Palova-Jelinkova, Lenka; Spisek, Radek

    High hydrostatic pressure (HHP) has been known to affect biological systems for >100 years. In this review, we describe the technology of HHP and its effect macromolecules and physiology of eukaryotic cells. We discuss the use of HHP in cancer immunotherapy to kill tumor cells for generation of whole cell and dendritic cell-based vaccines. We further summarize the current use and perspectives of HHP application in biomedicine, specifically in orthopedic surgery and for the viral, microbial and protozoan inactivation to develop vaccines against infectious diseases. Copyright © 2018. Published by Elsevier Inc.

  8. Adoptive T cell therapy: Addressing challenges in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Yee Cassian

    2005-04-01

    Full Text Available Abstract Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.

  9. Large local reactions to insect stings.

    Science.gov (United States)

    Golden, David B K

    2015-01-01

    Large local reactions (LLRs) are IgE-mediated late-phase inflammatory reactions that can cause great morbidity but are associated with a relatively low risk of future anaphylaxis. Patients with LLR may benefit from consultation with an allergist to help clarify the relative risk, to plan the best treatment for future stings, and to determine whether or not to pursue testing or venom immunotherapy (VIT). The chance of anaphylaxis to future stings is Immunology. Published by Elsevier Inc. All rights reserved.

  10. Immunotherapy with mutated onchocystatin fails to enhance the efficacy of a sub-lethal oxytetracycline regimen against Onchocerca ochengi.

    Science.gov (United States)

    Bah, Germanus S; Tanya, Vincent N; Makepeace, Benjamin L

    2015-08-15

    worm viability, dermal microfilarial density, anti-onchocystatin IgG in sera, and eosinophil counts in nodules. Only the gold-standard antibiotic regimen achieved significant killing of adult worms, a profound reduction in microfilarial load, and a sustained increase in local tissue eosinophilia. A small but statistically significant elevation in anti-onchocystatin IgG was observed for several weeks after immunisation in the immunotherapy-only group, but the antibody response in the immunochemotherapy group was more variable. At 12 weeks post-treatment, only a transient and non-significant increase in eosinophil counts was apparent in the immunochemotherapy group. We conclude that the addition of onchocystatin immunotherapy to a sub-lethal antibiotic regimen is insufficient to induce adulticidal activity, although with booster immunisations or the targeting of additional filarial immunomodulatory proteins, the efficacy of this strategy could be strengthened. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Antibody targeting of phosphatidylserine for the detection and immunotherapy of cancer

    Directory of Open Access Journals (Sweden)

    Belzile O

    2018-01-01

    Full Text Available Olivier Belzile,1 Xianming Huang,2,3 Jian Gong,2,3 Jay Carlson,2,3 Alan J Schroit,1 Rolf A Brekken,1 Bruce D Freimark2,3 1Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Preclinical Research, 3Department of Antibody Discovery, Peregrine Pharmaceuticals, Inc., Tustin, CA, USA Abstract: Phosphatidylserine (PS is a negatively charged phospholipid in all eukaryotic cells that is actively sequestered to the inner leaflet of the cell membrane. Exposure of PS on apoptotic cells is a normal physiological process that triggers their rapid removal by phagocytic engulfment under noninflammatory conditions via receptors primarily expressed on immune cells. PS is aberrantly exposed in the tumor microenvironment and contributes to the overall immunosuppressive signals that antagonize the development of local and systemic antitumor immune responses. PS-mediated immunosuppression in the tumor microenvironment is further exacerbated by chemotherapy and radiation treatments that result in increased levels of PS on dying cells and necrotic tissue. Antibodies targeting PS localize to tumors and block PS-mediated immunosuppression. Targeting exposed PS in the tumor microenvironment may be a novel approach to enhance immune responses to cancer. Keywords: immunosuppression, tumor microenvironment, immunotherapy, imaging, phosphatidylserine, bavituximab

  12. CTLA-4 blockade and the renaissance of cancer immunotherapy.

    Science.gov (United States)

    Mocellin, Simone; Nitti, Donato

    2013-12-01

    Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) plays a key role in restraining the adaptive immune response of T-cells towards a variety of antigens including tumor associated antigens (TAAs). The blockade of this immune checkpoint elicits an effective anticancer immune response in a range of preclinical models, suggesting that naturally occurring (or therapeutically induced) TAA specific lymphocytes need to be "unleashed" in order to properly fight against malignant cells. Therefore, investigators have tested this therapeutic hypothesis also in humans: the favorable results obtained with this strategy in patients with advanced cutaneous melanoma are revolutionizing the management of this highly aggressive disease and are fueling new enthusiasm on cancer immunotherapy in general. Here we summarize the biology of CTLA-4, overview the experimental data supporting the rational for targeting CTLA-4 to treat cancer and review the main clinical findings on this novel anticancer approach. Moreover, we critically discuss the current challenges and potential developments of this promising field of cancer immunotherapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. The Pathophysiology of Thyroid Eye Disease (TED): Implications for Immunotherapy

    Science.gov (United States)

    Gupta, Shivani; Douglas, Raymond

    2012-01-01

    Purpose of Review Thyroid eye disease (TED) is a poorly understood autoimmune manifestation most commonly associated with Graves’ disease. Current nonspecific treatment paradigms offer symptomatic improvement but fail to target the underlying pathogenic mechanisms and thus, do not significantly alter the long-term disease outcome. The purpose of this review is to provide an update of the current understanding of the immunopathogenesis of TED and explore these implications for targeted immunotherapy. Recent Findings Orbital fibroblasts are integral to the pathogenesis of TED and may modulate immune responses by production of cytokines and hyaluronan in response to activation of shared autoantigens including thyrotropin receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-R1). Fibrocytes share many of these phenotypic and functional features, suggesting a link between systemic and site-specific disease. Use of targeted immunotherapies in TED is limited, though data from the use Rituximab (RTX), a B cell depleting agent, are encouraging. Sustained clinical response has been seen with RTX in several reports, despite return of peripheral B cell levels to pretreatment levels. Additionally, this response appears to be independent to cytokine and antibody production, suggesting possible modulation of antigen presentation as a mechanism of its effect. Summary Progressive advances in the understanding of the immunopathogenesis of TED continue to spur clinical trials utilizing targeted immune therapies. Continued understanding of the molecular mechanisms of disease will expand potential treatments for TED patients and obviate the need for reconstructive surgical therapies. PMID:21730841

  14. Stability evaluation of house dust mite vaccines for sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    MARIJA GAVROVIĆ-JANKULOVIĆ

    2010-01-01

    Full Text Available Allergen-specific immunotherapy with house dust mite (HDM allergen extracts can effectively alleviate the symptoms of allergic rhinitis and asthma. The efficacy of the immunotherapeutic treatment is highly dependent on the quality of house dust mite vaccines. This study was performed to assess the stability of house dust mite allergen vaccines prepared for sublingual immunotherapy. Lyophilized Dermatophagoides pteronyssinus (Dpt mite bodies were the starting material for the production of sublingual vaccines in four therapeutic concentrations. The stability of the extract for vaccine production, which was stored below 4 °C for one month, showed consistence in the protein profile in SDS PAGE. ELISA-inhibition showed that the potencies of Dpt vaccines during a 12 month period were to 65–80 % preserved at all analyzed therapeutic concentrations. This study showed that glycerinated Dpt vaccines stored at 4 °C preserved their IgE-binding potential during a 12 month period, implying their suitability for sublingual immunotherapeutic treatment of HDM allergy.

  15. New Approaches to Immunotherapy for HPV Associated Cancers

    Directory of Open Access Journals (Sweden)

    Deepak Mittal

    2011-09-01

    Full Text Available Cervical cancer is the second most common cancer of women worldwide and is the first cancer shown to be entirely induced by a virus, the human papillomavirus (HPV, major oncogenic genotypes HPV-16 and -18. Two recently developed prophylactic cervical cancer vaccines, using virus-like particles (VLP technology, have the potential to prevent a large proportion of cervical cancer associated with HPV infection and to ensure long-term protection. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and do not prevent their progression to HPV-associated malignancy. In animal models, therapeutic vaccines for persisting HPV infection can eliminate transplantable tumors expressing HPV antigens, but are of limited efficacy in inducing rejection of skin grafts expressing the same antigens. In humans, clinical trials have reported successful immunotherapy of HPV lesions, providing hope and further interest. This review discusses possible new approaches to immunotherapy for HPV associated cancer, based on recent advances in our knowledge of the immunobiology of HPV infection, of epithelial immunology and of immunoregulation, with a brief overview on previous and current HPV vaccine clinical trials.

  16. Immunotherapy for Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Moskovitz, Jessica; Moy, Jennifer; Ferris, Robert L

    2018-03-03

    Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents. Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR). The anti PD1 agent, nivolumab, was recently approved by the FDA as a standard of care regimen for patients with platinum refractory recurrent/metastatic (R/M) HNSCC. Molecular pathways leading to resistance are starting to be identified, and work is underway to understand the most optimal treatment regimen with incorporation of immunotherapy. ICR has renewed interest in the immunology of cancer, but resistance is not uncommon, and thus understanding of these mechanisms will allow the clinician to appropriately select patients that will benefit from this therapy.

  17. Food allergy to apple and specific immunotherapy with birch pollen

    DEFF Research Database (Denmark)

    Hansen, K.S.; Khinchi, M.S.; Skov, P.S.

    2004-01-01

    Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic......Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen......-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open...... oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6...

  18. Designer exosomes as next-generation cancer immunotherapy.

    Science.gov (United States)

    Bell, Brandon M; Kirk, Isabel D; Hiltbrunner, Stefanie; Gabrielsson, Susanne; Bultema, Jarred J

    2016-01-01

    Exosomes are small 40-120 nm vesicles secreted by nearly all cells and are an important form of intercellular communication. Exosomes are abundant, stable, and highly bioavailable to tissues in vivo. Increasingly, exosomes are being recognized as potential therapeutics as they have the ability to elicit potent cellular responses in vitro and in vivo. Patient-derived exosomes have been employed as a novel cancer immunotherapy in several clinical trials, but at this point lack sufficient efficacy. Still other researchers have focused on modifying the content and function of exosomes in various ways, toward the end-goal of specialized therapeutic exosomes. Here we highlight major advances in the use of exosomes for cancer immunotherapy and exosome bioengineering followed by a discussion of focus areas for future research to generate potent therapeutic exosomes. From the Clinical Editor: Exosomes are small vesicles used by cells for intercellular communication. In this short article, the authors described the current status and the potential use of exosomes in the clinical setting. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. A STING-activating nanovaccine for cancer immunotherapy

    Science.gov (United States)

    Luo, Min; Wang, Hua; Wang, Zhaohui; Cai, Haocheng; Lu, Zhigang; Li, Yang; Du, Mingjian; Huang, Gang; Wang, Chensu; Chen, Xiang; Porembka, Matthew R.; Lea, Jayanthi; Frankel, Arthur E.; Fu, Yang-Xin; Chen, Zhijian J.; Gao, Jinming

    2017-07-01

    The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes. This effect is dependent on stimulator of interferon genes (STING), but not the Toll-like receptor or the mitochondrial antiviral-signalling protein (MAVS) pathway. The nanovaccine led to potent tumour growth inhibition in melanoma, colon cancer and human papilloma virus-E6/E7 tumour models. The combination of the PC7A nanovaccine and an anti-PD-1 antibody showed great synergy, with 100% survival over 60 days in a TC-1 tumour model. Rechallenging of these tumour-free animals with TC-1 cells led to complete inhibition of tumour growth, suggesting the generation of long-term antitumour memory. The STING-activating nanovaccine offers a simple, safe and robust strategy in boosting anti-tumour immunity for cancer immunotherapy.

  20. Tumor inherent interferons: Impact on immune reactivity and immunotherapy.

    Science.gov (United States)

    Brockwell, Natasha K; Parker, Belinda S

    2018-04-19

    Immunotherapy has revolutionized cancer treatment, with sustained responses to immune checkpoint inhibitors reported in a number of malignancies. Such therapeutics are now being trialed in aggressive or advanced cancers that are heavily reliant on untargeted therapies, such as triple negative breast cancer. However, responses have been underwhelming to date and are very difficult to predict, leading to an inability to accurately weigh up the benefit-to-risk ratio for their implementation. The tumor immune microenvironment has been closely linked to immunotherapeutic response, with superior responses observed in patients with T cell-inflamed or 'hot' tumors. One class of cytokines, the type I interferons, are a major dictator of tumor immune infiltration and activation. Tumor cell inherent interferon signaling dramatically influences the immune microenvironment and the expression of immune checkpoint proteins, hence regulators and targets of this pathway are candidate biomarkers of immunotherapeutic response. In support of a link between IFN signaling and immunotherapeutic response, the combination of type I interferon inducers with checkpoint immunotherapy has recently been demonstrated critical for a sustained anti-tumor response in aggressive breast cancer models. Here we review evidence that links type I interferons with a hot tumor immune microenvironment, response to checkpoint inhibitors and reduced risk of metastasis that supports their use as biomarkers and therapeutics in oncology. Copyright © 2018. Published by Elsevier Ltd.

  1. Regulatory T Cells: Potential Target in Anticancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Chi-Mou Juang

    2007-09-01

    Full Text Available The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

  2. Immunotherapy in urothelial cancer: recent data and perspectives

    Directory of Open Access Journals (Sweden)

    M. I. Volkova

    2017-01-01

    Full Text Available Immune-checkpoint inhibitors blocking the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1 and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4 have shown a prominent anti-tumor activity with long-term responses and an acceptable toxicity profile  in clinical trials. Pembrolizumab, atezolizumab, nivolumab, avelumab, and durvalumab are anti-PD-1/PD-L1 agents that redefine the standard of care for advanced urothelial carcinoma. CTLA-4 inhibitors are also under investigation in this setting. Phase III trial KEYNOTE-045 has demonstrated significant survival benefit in patients treated with pembrolizumab comparing with the standard second-line chemotherapy. Atezolizumab, nivolumab, avelumab, and durvalumab were also recommended for platinum-pretreated urothelial carcinoma patients based on phase II data. Following investigations of biomarkers such as PD-L1 expression are needed to determine high-responders to immunotherapy. This review article describes the advances in immunotherapy with immune-checkpoint inhibitors.

  3. Immunotherapy in pancreatic cancer: Unleash its potential through novel combinations.

    Science.gov (United States)

    Guo, Songchuan; Contratto, Merly; Miller, George; Leichman, Lawrence; Wu, Jennifer

    2017-06-10

    Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses. However, single checkpoint blockade was ineffective in pancreatic cancer, highlighting the challenges including the poor antigenicity, a dense desmoplastic stroma, and a largely immunosuppressive microenvironment. In this review, we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy, radiotherapy, and targeted therapy. These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.

  4. Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders.

    Science.gov (United States)

    McLaughlin, Lauren P; Bollard, Catherine M; Keller, Michael

    2017-01-01

    Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens. Thus, the emergence of adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is an attractive option for addressing the underlying impaired T cell immunity in many PID patients. VSTs have been utilized for PID patients following HSCT in many prior phase I trials, and may potentially be beneficial before HSCT in patients with chronic viral infections. We review the various methods of generating VSTs, clinical experience using VSTs for PID patients, and current limitations as well as potential ways to broaden the clinical applicability of adoptive immunotherapy for PID patients.

  5. DermAll nanomedicine for allergen-specific immunotherapy.

    Science.gov (United States)

    Garaczi, Edina; Szabó, Kornélia; Francziszti, László; Csiszovszki, Zsolt; Lőrincz, Orsolya; Tőke, Enikő R; Molnár, Levente; Bitai, Tamás; Jánossy, Tamás; Bata-Csörgő, Zsuzsanna; Kemény, Lajos; Lisziewicz, Julianna

    2013-11-01

    Allergen-specific immunotherapy (ASIT) the only disease-modifying treatment for IgE-mediated allergies is characterized with long treatment duration and high risk of side effects. We investigated the safety, immunogenicity and efficacy of a novel ASIT, called DermAll, in an experimental allergic rhinitis model. We designed and characterized DermAll-OVA, a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin (OVA) as model allergen. DermAll-OVA was administered topically with DermaPrep device to target Langerhans cells. To detect the clinical efficacy of DermAll ASIT we quantified the nasal symptoms and characterized the immunomodulatory activity of DermAll ASIT by measuring cytokine secretion after OVA-stimulation of splenocytes and antibodies from the sera. In allergic mice DermAll ASIT was as safe as Placebo, balanced the allergen-induced pathogenic TH2-polarized immune responses, and decreased the clinical symptoms by 52% [32%, 70%] compared to Placebo. These studies suggest that DermAll ASIT is safe and should significantly improve the immunopathology and symptoms of allergic diseases. A novel allergen-specific immunotherapy for IgE-mediated allergies is presented in this paper, using an experimental allergic rhinitis model and a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin as model allergen. Over 50% reduction of symptoms was found as the immune system's balance was favorably altered toward more TH2-polarized immune responses. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Current clinical trials testing combinations of immunotherapy and radiation.

    Science.gov (United States)

    Crittenden, Marka; Kohrt, Holbrook; Levy, Ronald; Jones, Jennifer; Camphausen, Kevin; Dicker, Adam; Demaria, Sandra; Formenti, Silvia

    2015-01-01

    Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an abscopal effect. Granulocyte-macrophage colony-stimulating factor was administered during radiotherapy to a metastatic site in patients with metastatic solid tumors to translate evidence obtained in a murine model of syngeneic mammary carcinoma treated with cytokine FLT-3L and radiation. Subsequent clinical availability of vaccines and immune checkpoint inhibitors has triggered a wave of enthusiasm for testing them in combination with radiotherapy. Examples of ongoing clinical trials are described in this report. Importantly, most of these trials include careful immune monitoring of the patients enrolled and will generate important data about the proimmunogenic effects of radiation in combination with a variety of immune modulators, in different disease settings. Results of these studies are building a platform of evidence for radiotherapy as an adjuvant to immunotherapy and encourage the growth of this novel field of radiation oncology. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The incidence of radiation necrosis following stereotactic radiotherapy for melanoma brain metastases: the potential impact of immunotherapy.

    Science.gov (United States)

    Kaidar-Person, Orit; Zagar, Timothy M; Deal, Allison; Moschos, Stergios J; Ewend, Matthew G; Sasaki-Adams, Deanna; Lee, Carrie B; Collichio, Frances A; Fried, David; Marks, Lawrence B; Chera, Bhishamjit S

    2017-07-01

    Stereotactic radiotherapy (SRT) is the standard treatment for patients with limited number of brain metastases. In the past few years, newer immunotherapies (immune checkpoint inhibitors) have been proven to prolong survival in patients with metastatic melanoma. The safety of the combination of SRT and immunotherapy for brain metastases is unknown. We retrospectively identified patients with melanoma brain metastases treated with SRT between 2007 and 2015. Patients who did not have at least 3 months of follow-up with imaging after SRT were excluded from the analysis. Outcomes were compared between patients who were treated with or without immunotherapy. A total of 58 patients were included; of these, 29 were treated with SRT and immunotherapy. MAPK inhibitors (BRAF, MEK inhibitors) were used more often in the immunotherapy group (nine vs. two patients). There was a higher incidence of intracranial complications in patients treated with immunotherapy and SRT. Eight patients had radiation necrosis; all occurred in patients who were treated with immunotherapy. Nine patients had hemorrhage, of which seven occurred in patients who were treated with immunotherapy (P=0.08). However, patients treated with immunotherapy and SRT had a significant overall survival advantage compared with SRT without immunotherapy (15 vs. 6 months, P=0.0013). Patients treated with SRT and immunotherapy have a higher incidence/risk of intracranial complications, but a longer overall survival.

  8. Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

    Science.gov (United States)

    Gutiérrez Fernández, D; Moreno-Ancillo, A; Fernández Meléndez, S; Domínguez-Noche, C; Gálvez Ruiz, P; Alfaya Arias, T; Carballada González, F; Alonso Llamazares, A; Marques Amat, L; Vega Castro, A; Antolín Amérigo, D; Cruz Granados, S; Ruiz León, B; Sánchez Morillas, L; Fernández Sánchez, J; Soriano Gomis, V; Borja Segade, J; Dalmau Duch, G; Guspi Bori, R; Miranda Páez, A

    2016-01-01

    Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

  9. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target.

    Science.gov (United States)

    Manguso, Robert T; Pope, Hans W; Zimmer, Margaret D; Brown, Flavian D; Yates, Kathleen B; Miller, Brian C; Collins, Natalie B; Bi, Kevin; LaFleur, Martin W; Juneja, Vikram R; Weiss, Sarah A; Lo, Jennifer; Fisher, David E; Miao, Diana; Van Allen, Eliezer; Root, David E; Sharpe, Arlene H; Doench, John G; Haining, W Nicholas

    2017-07-27

    Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy. Tumours were sensitized to immunotherapy by deletion of genes involved in several diverse pathways, including NF-κB signalling, antigen presentation and the unfolded protein response. In addition, deletion of the protein tyrosine phosphatase PTPN2 in tumour cells increased the efficacy of immunotherapy by enhancing interferon-γ-mediated effects on antigen presentation and growth suppression. In vivo genetic screens in tumour models can identify new immunotherapy targets in unanticipated pathways.

  10. Scope for innovation in immunotherapy from the financial market's point of view: Phacilitate Immunotherapy Leaders' Forum 2012.

    Science.gov (United States)

    Zilian, Olav

    2012-10-01

    In the vast area of immunotherapies, the development of monoclonal antibodies as a therapeutic concept emerged as a quantum leap out of the area of traditional vaccines (Köhler and Milstein) in vitro selection and optimisation made it possible to elaborate a single biological molecule from the molecular plethora of an individual adaptive immune response and to utilize such a cloned antibody repeatedly in a generalized fashion whenever the therapeutic indication is given to humans. At present, some 25 therapeutic monoclonal antibodies are currently being marketed in oncology, exceeding sales of USD20bn in 2011. A total of about 270 antibodies are currently in Phase II and III clinical development. Working on the assumption of usually lower attrition rates for antibody candidates, we expect approximately 120 of these 270 antibodies to be finally approved. This poses some key questions. What level of differentiation is required so that the coming new antibody drugs can command premium pricing when members of the founding generation become generic and inexpensive? What will global demand for antibody drugs be in view of the rising buying power in emerging pharmaceutical ('pharmerging') markets, but which is still not comparable with that of developed ones? What would the next quantum leaps be that might potentially push antibody technology on to a next level by disruptive innovation? Presentations given at the Phacilitate Immunotherapy Leaders' Forum 2012 (9-11 May in Barcelona) reflected on these questions and provided some stimulating perspectives.

  11. Induction of Immunogenic Cell Death with Non-Thermal Plasma for Cancer Immunotherapy

    Science.gov (United States)

    Lin, Abraham G.

    treatment, ROS immediately increased. When chemical attenuators of ROS were used, intracellular ROS was abrogated and emission of ICD markers were attenuated. This strongly suggests that plasma-induced ICD is associated with increased intracellular ROS. The gold-standard approach to evaluating whether a stimulus can elicit genuine ICD relies on a vaccination assay. CT26 colorectal cancer cells were treated at ICD-inducing regimes of plasma and injected into syngeneic Balb/c mice. One week later, mice were challenged with live CT26 cancer cells. Tumor progression was moderated in animals immunized with plasma-treated CT26 cells. Altogether, these provide strong evidence that plasma regimes can be adapted for a new application: ICD induction. Next, a study was conducted to test the potential of plasma to induce ICD in tumors in animals. Plasma treatment of subcutaneous tumors in mice elicited the emission of ecto-CRT and high mobility group box 1 (HMGB1), another marker of ICD, in the tumor and also recruited CD11c+ and CD45+ immune cells locally. This was followed by development of cancer-specific splenic T cells, indicating that a systemic anti-tumor response was elicited from localized plasma treatment of the tumor. Overall, this work demonstrates the development of non-thermal plasma as a novel method of inducing immunogenic cell death for cancer immunotherapy. The obtained results further our understanding of plasma-cellular interaction mechanisms and highlight the potential for clinical translation.

  12. Rapid Eye Movement Sleep Behavior Disorder in Paraneoplastic Cerebellar Degeneration: Improvement with Immunotherapy.

    Science.gov (United States)

    Vale, Thiago Cardoso; Fernandes do Prado, Lucila Bizari; do Prado, Gilmar Fernandes; Povoas Barsottini, Orlando Graziani; Pedroso, José Luiz

    2016-01-01

    To report two female patients with paraneoplastic cerebellar degeneration (PCD) related to breast cancer that presented with rapid eye movement-sleep behavior disorder (RBD) and improved sleep symptoms with immunotherapy. The two patients were evaluated through clinical scale and polysomnography before and after therapy with intravenous immunoglobulin. RBD was successfully treated with immunotherapy in both patients. Score on the RBD screening questionnaire dropped from 10 to 1 or 0, allied with the normalization of polysomnographic findings. A marked improvement in RBD after immunotherapy in PCD raises the hypothesis that secondary RBD may be an immune-mediated sleep disorder. © 2016 Associated Professional Sleep Societies, LLC.

  13. Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells.

    Science.gov (United States)

    Shen, Haifa; Sun, Tong; Hoang, Hanh H; Burchfield, Jana S; Hamilton, Gillian F; Mittendorf, Elizabeth A; Ferrari, Mauro

    2017-12-01

    Cancer immunotherapy has become arguably the most promising advancement in cancer research and therapy in recent years. The efficacy of cancer immunotherapy is critically dependent on specific physiological and physical processes - collectively referred to as transport barriers - including the activation of T cells by antigen presenting cells, T cells migration to and penetration into the tumor microenvironment, and movement of nutrients and other immune cells through the tumor microenvironment. Nanotechnology-based approaches have great potential to help overcome these transport barriers. In this review, we discuss the ways that nanotechnology is being leveraged to improve the efficacy and potency of various cancer immunotherapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Amyloid-beta immunotherapy: the hope for Alzheimer disease?

    Science.gov (United States)

    Barrera-Ocampo, Alvaro; Lopera, Francisco

    2016-12-30

    Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.

  15. Challenges and future perspectives of T cell immunotherapy in cancer

    Science.gov (United States)

    de Aquino, Maria Teresa P; Malhotra, Anshu; Mishra, Manoj K; Shanker, Anil

    2015-01-01

    Since the formulation of the tumour immunosurveillance theory, considerable focus has been on enhancing the effectiveness of host antitumour immunity, particularly with respect to T cells. A cancer evades or alters the host immune response by various ways to ensure its development and survival. These include modifications of the immune cell metabolism and T cell signaling. An inhibitory cytokine milieu in the tumour microenvironment also leads to immune suppression and tumour progression within a host. This review traces the development in the field and attempts to summarize the hurdles that the approach of adoptive T cell immunotherapy against cancer faces, and discusses the conditions that must be improved to allow effective eradication of cancer. PMID:26096822

  16. Exosomes in Cancer Nanomedicine and Immunotherapy: Prospects and Challenges.

    Science.gov (United States)

    Syn, Nicholas L; Wang, Lingzhi; Chow, Edward Kai-Hua; Lim, Chwee Teck; Goh, Boon-Cher

    2017-07-01

    Exosomes (versatile, cell-derived nanovesicles naturally endowed with exquisite target-homing specificity and the ability to surmount in vivo biological barriers) hold substantial promise for developing exciting approaches in drug delivery and cancer immunotherapy. Specifically, bioengineered exosomes are being successfully deployed to deliver potent tumoricidal drugs (siRNAs and chemotherapeutic compounds) preferentially to cancer cells, while a new generation of exosome-based therapeutic cancer vaccines has produced enticing results in early-phase clinical trials. Here, we review the state-of-the-art technologies and protocols, and discuss the prospects and challenges for the clinical development of this emerging class of therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    Science.gov (United States)

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

  18. Stabilizing human regulatory T cells for tolerance inducing immunotherapy.

    Science.gov (United States)

    He, Xuehui; Koenen, Hans Jpm; Slaats, Jeroen Hr; Joosten, Irma

    2017-08-01

    Many autoimmune diseases develop as a consequence of an altered balance between autoreactive immune cells and suppressive FOXP3 + Treg. Restoring this balance through amplification of Treg represents a promising strategy to treat disease. However, FOXP3 + Treg might become unstable especially under certain inflammatory conditions, and might transform into proinflammatory cytokine-producing cells. The issue of heterogeneity and instability of Treg has caused considerable debate in the field and has important implications for Treg-based immunotherapy. In this review, we discuss how Treg stability is defined and what the molecular mechanisms underlying the maintenance of FOXP3 expression and the regulation of Treg stability are. Also, we elaborate on current strategies used to stabilize human Treg for clinical purposes. This review focuses on human Treg, but considering that cell-intrinsic mechanisms to regulate Treg stability in mice and in humans might be similar, data derived from mice studies are also discussed in this paper.

  19. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer

    Directory of Open Access Journals (Sweden)

    Waldemar Białek

    2016-12-01

    Full Text Available Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

  20. Development of nanoparticle based delivery systems for sublingual immunotherapy

    DEFF Research Database (Denmark)

    Alija, Hava; Rask, Carola; Brimnes, Jens

    The prevalence of IgE mediated allergic diseases is increasing dramatically in industrialized countries. Sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficacious treatment for IgE mediated allergic diseases, but requires protracted treatment duration. Even though SLIT...... (OVA)-induced allergic airway inflammation model for their ability to improve immune tolerance induction of ovalbumin (protein and peptide) when delivered sublingually. In the liposome study, mice were treated sublingually during two weeks with free or liposome encapsulated OVA (OVA-liposomes) followed...... by intraperitoneal injections and intranasal challenge. Mice treated sublingually with OVA-liposomes showed a significant reduction of airway eosinophilia, OVA-specific IgE antibodies and splenocyte proliferation in comparison to free OVA. In addition, reduced levels of IFN-ɣ and IL-5 were observed in spleen cell...

  1. Trial Watch: Immunotherapy plus radiation therapy for oncological indications.

    Science.gov (United States)

    Vacchelli, Erika; Bloy, Norma; Aranda, Fernando; Buqué, Aitziber; Cremer, Isabelle; Demaria, Sandra; Eggermont, Alexander; Formenti, Silvia Chiara; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2016-01-01

    Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects. Here, we summarize recent preclinical and clinical advances in this field of investigation.

  2. Pathogenesis and immunotherapy in cutaneous psoriasis: what can rheumatologists learn?

    Science.gov (United States)

    Alexander, Helen; Nestle, Frank O

    2017-01-01

    This review presents our current understanding of the pathogenesis and treatment of psoriasis with a particular focus on recent areas of research and emerging concepts. Psoriasis arises in genetically predisposed individuals who have an abnormal innate and adaptive immune response to environmental factors. Recent studies have identified novel genetic, epigenetic and immunological factors that play a role in the disease pathogenesis. There is emerging evidence for the role of the skin microbiome in psoriasis. Studies have shown reduced diversity and altered composition of the skin microbiota in psoriasis. Recent advances in our understanding of the complex immunopathogenesis of psoriasis have led to the identification of crucial cytokines and cell signalling pathways that are targeted by a range of immunotherapies.

  3. Neutrophils and Granulocytic MDSC: The Janus God of Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Serena Zilio

    2016-09-01

    Full Text Available Neutrophils are the most abundant circulating blood cell type in humans, and are the first white blood cells recruited at the inflammation site where they orchestrate the initial immune response. Although their presence at the tumor site was recognized in the 1970s, until recently these cells have been neglected and considered to play just a neutral role in tumor progression. Indeed, in recent years neutrophils have been recognized to play a dual role in tumor development by either assisting the growth, angiogenesis, invasion, and metastasis or by exerting tumoricidal action directly via the secretion of antitumoral compounds, or indirectly via the orchestration of antitumor immunity. Understanding the biology of these cells and influencing their polarization in the tumor micro- and macro-environment may be the key for the development of new therapeutic strategies, which may finally hold the promise of an effective immunotherapy for cancer.

  4. Guiding principles of subcutaneous immunotherapy for allergic rhinitis in Japan.

    Science.gov (United States)

    Okamoto, Yoshitaka; Ohta, Nobuo; Okano, Mitsuhiro; Kamijo, Atsushi; Gotoh, Minoru; Suzuki, Motohiko; Takeno, Sachio; Terada, Tetsuya; Hanazawa, Toyoyuki; Horiguchi, Shigetoshi; Honda, Kohei; Matsune, Shoji; Yamada, Takechiyo; Yuta, Atsushi; Nakayama, Takeo; Fujieda, Shigeharu

    2014-02-01

    In anticipation of the development of guidelines for antigen-specific subcutaneous immunotherapy (SCIT), we present recommendations that can serve as guiding principles based on a review of the scientific literature. Clinical questions (CQs) concerning SCIT were prepared. Literature searches for publications between January 1990 and February 2011 were performed in PubMed, the Cochrane Library, and Japana Centra Revuo Medicina Web version 4. Qualified studies were analyzed and the results were evaluated, consolidated, and codified. We present answers for 13 CQs on the indications, methods, effectiveness and mechanisms of SCIT, with evidence-based recommendations. The guiding principles are intended to be applied to children (≤15 years old) and adults (≥16 years old) with allergic rhinitis (AR). These principles can be used by otorhinolaryngologists for diagnosis of AR, evaluation of severity and rhinoscopic findings, performance of antigen challenge tests, and management of systemic anaphylactic reactions associated with SCIT. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

    Science.gov (United States)

    Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

    2014-01-01

    Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

  6. Synthetic biology in cell-based cancer immunotherapy.

    Science.gov (United States)

    Chakravarti, Deboki; Wong, Wilson W

    2015-08-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. We first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Pretargeting immunotherapy: a novel treatment approach for systemic amyloidosis.

    Science.gov (United States)

    Wall, Jonathan S; Foster, James S; Martin, Emily B; Kennel, Stephen J

    2017-09-01

    The amyloidoses are a complex group of disorders characterized by the deposition of proteinaceous amyloid fibrils in vital organs. The deposits are nonimmunogenic and may be composed of one of more than 35 proteins. We have developed a two-stage immunotherapeutic approach using peptides that recognize most, if not all, amyloid deposits to facilitate amyloid clearance. In the first embodiment, we have developed a bifunctional peptope to enhance and expand the utility of currently available antibodies. In the second, we have generated peptide-reactive antibodies that can be targeted to the amyloid deposits by peptides thereby providing alternative reagents for immunotherapy of amyloidosis. These technologies provide tools for treating the many forms of amyloid disease, restoring organ function and enhancing patient survival.

  8. Antibody-mediated immunotherapy against chronic hepatitis B virus infection.

    Science.gov (United States)

    Gao, Ying; Zhang, Tian-Ying; Yuan, Quan; Xia, Ning-Shao

    2017-08-03

    The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogs, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus. As an alternative strategy, immunotherapy with HBsAg-specific antibodies has shown some direct HBsAg suppression effects in several preclinical and clinical trial studies. However, most described previously HBsAg-specific antibodies only had very short-term HBsAg suppression effects in CHB patients and animal models mimicking persistent HBV infection. More-potent antibodies with long-lasting HBsAg clearance effects are required for the development of the clinical application of antibody-mediated immunotherapy for CHB treatment. Our recent study described a novel mAb E6F6 that targets a unique epitope on HBsAg. It could durably suppress the levels of HBsAg and HBV DNA via Fcγ receptor-dependent phagocytosis in vivo. In this commentary, we summarize the current research progress, including the therapeutic roles and mechanisms of antibody-mediated HBV clearance as well as the epitope-determined therapeutic potency of the antibody. These insights may provide some clues and guidance to facilitate the development of therapeutic antibodies against persistent viral infection.

  9. ErbB-targeted CAR T-cell immunotherapy of cancer.

    Science.gov (United States)

    Whilding, Lynsey M; Maher, John

    2015-01-01

    Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

  10. Disparities of Immunotherapy Utilization in Patients with Stage III Cutaneous Melanoma: A National Perspective.

    Science.gov (United States)

    Al-Qurayshi, Zaid; Crowther, Jason E; Hamner, John B; Ducoin, Christopher; Killackey, Mary T; Kandil, Emad

    2018-05-01

    Immunotherapy combined with surgery is associated with better survival than surgery alone in patients with advanced melanoma. This study examined the utilization of immunotherapy in relation to population characteristics and the associated survival benefit. This was a retrospective cohort study utilizing the US National Cancer Database. The study population included 6,165 adult patients (≥18 years) with stage III cutaneous melanoma (median follow-up=32 months). A total of 1,854 patients underwent immunotherapy in addition to surgery, which was associated with a survival benefit over surgery alone (hazard ratio(HR)=0.66, 95% confidence interval(CI)=0.56-0.77, pimmunotherapy utilization (all pimmunotherapy usage was found (p=0.07). Compared to other demographic factors, insurance status was associated with the greatest disparities in immunotherapy utilization and mortality for patients who underwent surgery for advanced melanoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Functional evaluation of bone marrow derived DC of tumor bearing mice after immunotherapy

    International Nuclear Information System (INIS)

    Li Min; Chen Cheng; Gu Tao; Zhou Huan; Zhang Feng; Zhu Yibei; Yu Gehua; Zhang Xueguang; Gu Zongjiang

    2006-01-01

    Objective: To evaluate the function of bone marrow derived DC of tumor bearing mice after immunotherapy. Methods: Tumor bearing mice were immunized with DC vaccine plus injection of agonistic anti-4-1BB monoclonal antibody. The proliferation of T cells primed with bone marrow derived DC of tumor bearing mice after immunotherapy was tested by 3 H-TdR incorporation. ELISA was employed to determine the levels of IL-2, IFN-γ and IL-10 secreted by DC primed T cells. Results: Bone marrow derived DC of tumor bearing mice was less efficient in stimulating the proliferation of T cells and IL-2 and IFN-γ secretion made by T cells. After immunotherapy, the proliferation of cells and IL-2 and IFN-γ secretionmade by T cells were enhanced. Conclusion: The function of bone marrow derived DC of tumor bearing mice after immunotherapy was ameliorated. (authors)

  12. Allergen immunotherapy for allergic rhinoconjunctivitis : A systematic overview of systematic reviews

    NARCIS (Netherlands)

    Nurmatov, Ulugbek; Dhami, Sangeeta; Arasi, Stefania; Roberts, Graham; Pfaar, Oliver; Muraro, Antonella; Ansotegui, Ignacio J; Calderon, Moises; Cingi, Cemal; Durham, Stephen; van Wijk, Roy Gerth; Halken, Susanne; Hamelmann, Eckard; Hellings, Peter W; Jacobsen, Lars; Knol, Edward; Larenas-Linnemann, Desiree; Lin, Sandra Y; Maggina, Vivian; Oude Elberink, J Hanneke N G; Pajno, Giovanni Battista; Panwankar, Ruby; Pastorello, Elideanna; Pitsios, Constantinos; Rotiroti, Giuseppina; Timmermans, Frans; Tsilochristou, Olympia; Varga, Eva-Maria; Wilkinson, Jamie; Williams, Andrew; Worm, Margitta; Zhang, Luo; Sheikh, Aziz

    2017-01-01

    Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the

  13. Enhancing the Effectiveness of Breast Cancer Immunotherapy through Manipulation of the T Cell Cytoskeleton

    National Research Council Canada - National Science Library

    Ratner, Stuart

    2002-01-01

    Adoptive immunotherapy, the in vitro activation and infusion of patient T cells, is a potentially useful immunotherapeutic strategy, but its effectiveness is limited by the poor trafficking and tumor...

  14. Critical appraisal of the clinical utility of sublingual immunotherapy in allergy

    Directory of Open Access Journals (Sweden)

    S. Aissa

    2016-12-01

    We performed a literature review in order to remind the mechanisms of action and to demonstrate efficacy and tolerability of the sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma and its impact on the quality of life.

  15. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    International Nuclear Information System (INIS)

    Li Xiaosong; Hode, Tomas; Guerra, Maria C; Ferrel, Gabriela L; Nordquist, Robert E; Chen, Wei R

    2011-01-01

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  16. Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0109 TITLE: Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Elizabeth A. Mittendorf, MD, PhD CONTRACTING ORGANIZATION: University of Texas MD Anderson Cancer Center Houston, TX 77030 REPORT DATE: October...CONTRACT NUMBER Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0109 5c. PROGRAM

  17. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma

    DEFF Research Database (Denmark)

    Jacobsen, L; Niggemann, B; Dreborg, S

    2007-01-01

    BACKGROUND: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. OBJECTIVE: We......: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination....

  18. Design and synthesis of multivalent glycoconjugates for anti-cancer immunotherapy

    OpenAIRE

    Pifferi , Carlo

    2017-01-01

    Cancer is one on the leading causes of death in developed countries; although surgical resection, direct irradiation and cytotoxic chemotherapy represent nowadays the main treatment options for patients suffering with malignancies, their severe side effects paved the way for the rise in popularity of antitumoral immunotherapy. Apart from passive immunotherapy, which is comprised of antibodies or other immune system components that are made outside of the body and has been shown to be associat...

  19. Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside

    OpenAIRE

    Saburi, Ehsan; Saburi, Amin; Ghanei, Mostafa

    2017-01-01

    Immunotherapy has been used for years in many types of cancer therapy. Recently, cancer immunotherapy has focused on mechanisms which can enhance the development of cell-mediated immunity. Anticancer medications are administered to inhibit immunosuppressive factors such as nagalase enzyme, which is produced by neoplastic cells and destroys macrophage activating factor (Gc-MAF). Anti-neoplastics medications can also enhance immune-cell activity against tumors. Such medications show great poten...

  20. Treatment of Adults with Idiopathic Recurrent Pericarditis: Novel Use of Immunotherapy.

    Science.gov (United States)

    Schwier, Nicholas C; Hale, Genevieve M; Davies, Marie L

    2017-03-01

    Idiopathic recurrent pericarditis (IRP) can be challenging to treat. Even after guideline-directed first-line treatment consisting of aspirin (ASA) or a nonsteroidal antiinflammatory drug (NSAID) in combination with colchicine therapy, recurrences still occur in greater than 20% of patients. Many patients then require treatment with long-term corticosteroids, which is not a favorable option due to their short- and long-term adverse effects. Because it is theorized that the pathophysiology of IRP may possess autoimmune sequelae, the use of immunotherapy for the treatment of IRP has emerged. In this review, we describe the literature associated with immunotherapy used to treat IRP in an adult population as well as provide an overview of the safety and monitoring parameters for each agent. The most common immunotherapies used after patients have had multiple recurrences of IRP are anakinra, intravenous immunoglobulin (IVIG), and azathioprine. In most cases, these immunotherapies are adjunctive therapy, with the goal of tapering and discontinuing immunosuppressive corticosteroids. After reviewing the data, anakinra resulted in more patients discontinuing corticosteroids and prevented further recurrences of pericarditis. IVIG resulted in symptom resolution and no further recurrences in most of the patients. Azathioprine was associated with more than half of patients becoming recurrence free; however, many patients required a restart of corticosteroids due to recurrence. Clinicians should be aware of the adverse effects of immunotherapy, ranging from mild gastrointestinal events to risk of infection and serious blood dyscrasias that may require diligent monitoring. The use of immunotherapy for the treatment of adults with IRP should be restricted to patients who have multiple recurrences. Ideally, immunotherapy would be adjunctive to first-line combination therapy with ASA/NSAID plus colchicine, with the goal of tapering and discontinuing immunosuppressive

  1. Engineering Hematopoietic Cells for Cancer Immunotherapy: Strategies to Address Safety and Toxicity Concerns.

    Science.gov (United States)

    Resetca, Diana; Neschadim, Anton; Medin, Jeffrey A

    2016-09-01

    Advances in cancer immunotherapies utilizing engineered hematopoietic cells have recently generated significant clinical successes. Of great promise are immunotherapies based on chimeric antigen receptor-engineered T (CAR-T) cells that are targeted toward malignant cells expressing defined tumor-associated antigens. CAR-T cells harness the effector function of the adaptive arm of the immune system and redirect it against cancer cells, overcoming the major challenges of immunotherapy, such as breaking tolerance to self-antigens and beating cancer immune system-evasion mechanisms. In early clinical trials, CAR-T cell-based therapies achieved complete and durable responses in a significant proportion of patients. Despite clinical successes and given the side effect profiles of immunotherapies based on engineered cells, potential concerns with the safety and toxicity of various therapeutic modalities remain. We discuss the concerns associated with the safety and stability of the gene delivery vehicles for cell engineering and with toxicities due to off-target and on-target, off-tumor effector functions of the engineered cells. We then overview the various strategies aimed at improving the safety of and resolving toxicities associated with cell-based immunotherapies. Integrating failsafe switches based on different suicide gene therapy systems into engineered cells engenders promising strategies toward ensuring the safety of cancer immunotherapies in the clinic.

  2. Novel Immunotherapy Options for Extranodal NK/T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Boyu Hu

    2018-04-01

    patients including five with a complete response (CR. Furthermore, cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 have shown encouraging results with durable CRs as either maintenance therapy after initial induction chemotherapy or in the relapsed/refractory setting. In this paper, we review this exciting field of novel immunotherapy options against ENKTCL that hopefully will change the treatment paradigm in this deadly disease.

  3. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Hiniker, Susan M., E-mail: shiniker@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Reddy, Sunil A. [Division of Oncology, Department of Medicine, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Maecker, Holden T.; Subrahmanyam, Priyanka B.; Rosenberg-Hasson, Yael [Human Immune Monitoring Center, Institute for Immunity, Transplantation, and Infection, Stanford University Medical Center, Stanford, California (United States); Swetter, Susan M. [Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California (United States); Saha, Saurabh [Atlas Venture, Cambridge, Massachusetts (United States); Shura, Lei; Knox, Susan J. [Department of Radiation Oncology, Stanford University Medical Center and Cancer Institute, Stanford, California (United States)

    2016-11-01

    Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasis measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the

  4. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

    International Nuclear Information System (INIS)

    Hiniker, Susan M.; Reddy, Sunil A.; Maecker, Holden T.; Subrahmanyam, Priyanka B.; Rosenberg-Hasson, Yael; Swetter, Susan M.; Saha, Saurabh; Shura, Lei; Knox, Susan J.

    2016-01-01

    Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasis measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the

  5. Cancer immunotherapy: effect of local treatment on the growth of lung metastases

    Czech Academy of Sciences Publication Activity Database

    Šímová, Jana; Mikyšková, Romana; Mendoza, Luis; Jandlová, Táňa; Povýšil, C.; Bubeník, Jan

    2001-01-01

    Roč. 54, Suppl. 1 (2001), s. 131 ISSN 0300-9475. [International Congress of Immunology /11./. 22.07.2001-27.07.2001, Stockholm] Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology

  6. Local elevation of CCL22: A new trend in immunotherapy (skin model

    Directory of Open Access Journals (Sweden)

    Omer Yahia Elhussein Mohamed

    2016-11-01

    Full Text Available Many evidences supported the suggestion that one of the reasons for the failure of immunosuppressant like Corticosteroides, Calcinurine inhibitors and VitD3 in reestablishing skin immune tolerance is relying on inhibition of CCL22 expression from skin dendritic cells. Inhibition of CCL22 decreases CD4+ CD25+ FoxP3+ regulatory T cells homing to macular area and reduces the suppression capacity of these cells that make a sort of an imbalance between effector and regulatory T cells. Addition of CCL22 into the skin lesion from external sources could change the ratio between effector and regulatory T cells which dramatically alter immune system and reestablish immune tolerance. This action can't be established by the later immunosuppressant (e.g. corticosteroids and calcinurine inhibitors alone which give CCL22 an important role in the treatment of skin autoimmune and graft rejection diseases.

  7. Immunotherapy using dendritic cells and cytokine-induced killer for kidney cancer

    International Nuclear Information System (INIS)

    Chen Lijun; Xu Yuanbin; Zhao Li; Qu Nan; Sun Zhenpeng; Li Xuechao; Zhao Jiyu; Wang Bin; Wang Huixian

    2008-01-01

    Objective: To investigate the clinical efficacy of immunotherapy using dendritic cells (DC) and cytokine-induced killer (CIK)in treatment of patients with kidney cancer. Methods: Sixty patients with kidney cancer were divided into 2 groups randomly: the control group and immunotherapy group. Peripheral blood mononuclear cells (PBMC) were seperated from the patients who received immunotherapy first, then DC and CIK were induced and cultured with GM-CSF and IL4 in vitro. The immunotherapy group received DC four times and CIK twice at an interval of 14 days after routine treatment. The control group received only chemotherapy. T lymphocyte subtypes and NK cells in peripheral blood, the white cells and the values of liver and kidney biochemistry of two group of patients were analyzed and clinical efficacy were ob- served, so were side effects. Results: Clinical efficacy showed significant statistical difference between the two groups (P + , CD4 + , CD4 + /CD8 + and NK cell in the immunotherapy group increased after treatment, which showed significant statistical difference compared with those before treatment(P value was 0.010, 0.026, 0.021, 0.016, respectively). Changes in cell immune indexes (CD3 + , CD4 + , CD4 + /CD8 + ) in immunotherapy group and Control group showed significant statistical difference (P value was 0.001,0.023,0.012, respectively). Conclusion: Immunotherapy using dendritic cells and cytokine-induced killer combined with routine treatment can improve T lymphocyte subtypes and NK cell ratio in peripheral blood of the patients with kidney cancer, and may play an important role in the treatment of kidney cancer. It can enhance clinical efficacy in patients with kidney cancer and can improve prognosis. (authors)

  8. The application of natural killer (NK cell immunotherapy for the treatment of cancer

    Directory of Open Access Journals (Sweden)

    Rayne H Rouce

    2015-11-01

    Full Text Available Natural killer (NK cells are essential components of the innate immune system and play a critical role in host immunity against cancer. Recent progress in our understanding of NK cell immunobiology has paved the way for novel NK cell-based therapeutic strategies for the treatment of cancer. In this review, we will focus on recent advances in the field of NK cell immunotherapy, including augmentation of antibody-dependent cellular cytotoxicity, manipulation of receptor-mediated activation, and adoptive immunotherapy with ex vivo expanded, chimeric antigen receptor (CAR engineered or engager-modified NK cells. In contrast to T lymphocytes, donor NK cells do not attack non-hematopoietic tissues, suggesting that an NK-mediated anti-tumor effect can be achieved in the absence of graft-versus-host disease. Despite reports of clinical efficacy, a number of factors limit the application of NK cell immunotherapy for the treatment of cancer such as the failure of infused NK cells to expand and persist in vivo. Therefore efforts to enhance the therapeutic benefit of NK cell-based immunotherapy by developing strategies to manipulate the NK cell product, host factors and tumor targets are the subject of intense research. In the preclinical setting, genetic engineering of NK cells to express CARs to redirect their antitumor specificity has shown significant promise. Given the short lifespan and potent cytolytic function of mature NK cells, they are attractive candidate effector cells to express CARs for adoptive immunotherapies. Another innovative approach to redirect NK cytotoxicity towards tumor cells is to create either bispecific or trispecific antibodies, thus augmenting cytotoxicity against tumor-associated antigens. These are exciting times for the study of NK cells; with recent advances in the field of NK cell biology and translational research, it is likely that NK cell immunotherapy will move to the forefront of cancer immunotherapy over the next

  9. Priming anticancer active specific immunotherapy with dendritic cells.

    Science.gov (United States)

    Mocellin, Simone

    2005-06-01

    Dendritic cells (DCs) probably represent the most powerful naturally occurring immunological adjuvant for anticancer vaccines. However, the initial enthusiasm for DC-based vaccines is being tempered by clinical results not meeting expectations. The partial failure of current vaccine formulations is explained by the extraordinary complexity of the immune system, which makes the task of exploiting the potential of such a biotherapeutic approach highly challenging. Clinical findings obtained in humans so far indicate that the immune system can be actively polarized against malignant cells by means of DC-based active specific immunotherapy, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally 'dormant' immune effectors can actually be employed as endogenous weapons against malignant cells. Only the thorough understanding of DC biology and tumor-host immune system interactions will allow researchers to reproduce, in a larger set of patients, the cellular/molecular conditions leading to an effective immune-mediated eradication of cancer.

  10. Extensive necrosis of visceral melanoma metastases after immunotherapy

    Directory of Open Access Journals (Sweden)

    Poston Graeme J

    2008-03-01

    Full Text Available Abstract Background The prognosis for metastatic melanoma remains poor even with traditional decarbazine or interferon therapy. 5-year survival is markedly higher amongst patients undergoing metastatectomy. Unfortunately not all are suitable for metastatectomy. Alternative agents for systemic therapy have, to date, offered no greater rates of survival beyond traditional therapy. A toll-like receptor 9 agonist, PF-3512676 (formerly known as CPG 7909 is currently being evaluated for its potential. Case presentation We present the case of a 54-year-old Caucasian male with completely resected metastatic cutaneous melanoma after immunotherapy. The patient initially progressed during adjuvant high-dose interferon, with metastases to the liver, spleen, and pelvic lymph nodes. During an 18-month treatment period with PF-3512676 (formerly known as CPG 7909, a synthetic cytosine-phosphorothioate-guanine rich oligodeoxynucleotide, slow radiologic disease progression was demonstrated at the original disease sites. Subsequent excision of splenic and pelvic nodal metastases was performed, followed by resection of the liver metastases. Histologic examination of both hepatic and splenic melanoma metastases showed extensive necrosis. Subsequent disease-free status was demonstrated by serial positron emission tomography (PET. Conclusion Existing evidence from phase I/II trials suggests systemic treatment with PF-3512676 is capable of provoking a strong tumor-specific immune response and may account for the prolonged tumor control in this instance.

  11. Novel Antibody-Based Proteins for Cancer Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fuenmayor, Jaheli; Montaño, Ramon F., E-mail: jfuenmay@ivic.gob.ve [Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas. Caracas, 1020-A (Venezuela, Bolivarian Republic of)

    2011-08-19

    The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.

  12. Novel recombinant alphaviral and adenoviral vectors for cancer immunotherapy.

    Science.gov (United States)

    Osada, Takuya; Morse, Michael A; Hobeika, Amy; Lyerly, H Kim

    2012-06-01

    Although cellular immunotherapy based on autolgous dendritic cells (DCs) targeting antigens expressed by metastatic cancer has demonstrated clinical efficacy, the logistical challenges in generating an individualized cell product create an imperative to develop alternatives to DC-based cancer vaccines. Particularly attractive alternatives include in situ delivery of antigen and activation signals to resident antigen-presenting cells (APCs), which can be achieved by novel fusion molecules targeting the mannose receptor and by recombinant viral vectors expressing the antigen of interest and capable of infecting DCs. A particular challenge in the use of viral vectors is the well-appreciated clinical obstacles to their efficacy, specifically vector-specific neutralizing immune responses. Because heterologous prime and boost strategies have been demonstrated to be particularly potent, we developed two novel recombinant vectors based on alphaviral replicon particles and a next-generation adenovirus encoding an antigen commonly overexpressed in many human cancers, carcinoembryonic antigen (CEA). The rationale for developing these vectors, their unique characteristics, the preclinical studies and early clinical experience with each, and opportunities to enhance their effectiveness will be reviewed. The potential of each of these potent recombinant vectors to efficiently generate clinically active anti-tumor immune response alone, or in combination, will be discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    Energy Technology Data Exchange (ETDEWEB)

    Liechtenstein, Therese, E-mail: t.liechtenstein.12@ucl.ac.uk [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Perez-Janices, Noemi; Escors, David [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Navarrabiomed Fundacion Miguel Servet, 3 Irunlarrea St., Hospital Complex of Navarra, 31008 Pamplona, Navarra (Spain)

    2013-07-02

    The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

  14. Assays for predicting and monitoring responses to lung cancer immunotherapy

    International Nuclear Information System (INIS)

    Teixidó, Cristina; Karachaliou, Niki; González-Cao, Maria; Morales-Espinosa, Daniela; Rosell, Rafael

    2015-01-01

    Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 (PD-1) and its ligand (PD-L1), have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer (NSCLC). Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry (IHC) with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-1/PD-L1 pathway

  15. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    International Nuclear Information System (INIS)

    Liechtenstein, Therese; Perez-Janices, Noemi; Escors, David

    2013-01-01

    The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells

  16. Effect of SPG (Sonifilan) immunotherapy and PDT on murine tumor

    International Nuclear Information System (INIS)

    Korbelik, M.; Krosl, G.; Dougherty, G.J.; Chaplin, D.J.

    1992-01-01

    PhotoDynamic Therapy of solid tumors is unique in eliciting a strong host immune response unparalleled in other cancer therapies. This immune response is manifested as an acute inflammatory reaction, and can be readily seen as redness and edema around the treated area. Destruction of typical solid tumor cannot be accomplished solely by direct phototoxic action. This was shown to be the case even with drugs more potent in this direct killing effect than Photofrin, the photosensitizer presently used in clinical PDT. Limiting factors seem to be regional insufficiencies in supply of molecular oxygen, needed for generation of phototoxic species. They can be ascribed to the existence of chronically and acute hypoxic tumor regions, oxygen consumption by the photodynamic process, and vascular shutdown induced during PDT. The remaining tumor mass is eradicated by an indirect effect, necrosis induced by destruction of tumor vasculature. Since most events in PDT treated tumor that lead to vascular collapse are, in fact, typical inflammatory manifestations, it was suggested that PDT-induced acute inflammatory reaction actually leads to vascular damage. In a related report characteristics are shown of cellular inflammatory infiltrate in PDT-treated murine tumor. This work examines the effect of combining PDT with immunotherapy, in an attempt to investigate a possibility of amplification of immune reaction to PDT and its direction towards more pervasive destruction of treated tumors. (authors). 6 refs

  17. Effectiveness of leukocyte immunotherapy in primary recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Gharesi-Fard, Behrouz; Zolghadri, Jaleh; Foroughinia, Leila; Tavazoo, Fahimeh; Samsami Dehaghani, Alamtaj

    2007-09-01

    Recurrent spontaneous abortion (RSA) is defined as three or more sequential abortions before the twentieth week of gestation. There are evidences to support an allo-immunologic mechanism for RSA. One of the methods for treatment of RSA is leukocyte therapy; however there is still controversy about effectiveness of this method. To evaluate the effectiveness of leukocyte therapy for treatment of RSA. Ninety two non-pregnant women with at least three sequential abortions (60 primary & 32 secondary aborters) recognized as RSA were referred to our Laboratory for immunotherapy. All the cases were immunized by isolated lymphocytes from their husbands. Fifty to 100 million washed and resuspended mononuclear cells were injected by I.V., S.C., and I.D. route. The result of each injection was checked by WBC cross matching between couples after four weeks of injections. Immunization was repeated in fifth week to a maximum of 3 times if needed. Eighty one age-matched non-pregnant RSA women (52 primary and 29 secondary aborters) with at least three sequential abortions were also included in this study as controls. The control group was not immunized. 67 out of 92 (72.8%) immunized cases and 44 out of 81 controls (54.3%) showed a successful outcome of pregnancy (pRSA patients. Despite the current controversy and limitation of leukocyte therapy in RSA, the results of our investigation provide evidence supporting the use of allo-immunization in improving the outcome of pregnancy in primary RSA patients.

  18. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    Directory of Open Access Journals (Sweden)

    David Escors

    2013-07-01

    Full Text Available The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(g-retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and b-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

  19. The Use of Omalizumab in Food Oral Immunotherapy.

    Science.gov (United States)

    Labrosse, Roxane; Graham, François; Des Roches, Anne; Bégin, Philippe

    2017-06-01

    Food allergy is an important health issue that affects up to 8 % of the population. The management of allergic patients involves allergen avoidance and prompts the treatment of accidental reactions, as no curative treatment is available so far in routine practice. Oral immunotherapy (OIT) is a promising therapeutic alternative, but it is associated with frequent allergic reactions and cost-effectiveness issues. In hopes of reducing such reactions, a number of trials have used omalizumab, an anti-IgE monoclonal humanized antibody, as adjunctive therapy in OIT. The allergens studied in these omalizumab-enabled OIT trials include peanuts, milk, eggs, or mixes of multiple foods. In this article, we review the major findings from these studies and discuss potential benefits and issues related to omalizumab-enabled OIT. Results from the previous trials suggest that the use of omalizumab could potentially lead to safer and more efficient OIT protocols, by reducing the number and severity of reactions, and increasing allergen tolerance threshold. While more evidence is needed with regard to the maintenance of the long-term tolerance after OIT, omalizumab's potential immunomodulatory role could be of benefit. More studies are needed to further document this new indication for omalizumab.

  20. Immunotherapy for recurrent malignant glioma: an interim report on survival.

    Science.gov (United States)

    Ingram, M; Buckwalter, J G; Jacques, D B; Freshwater, D B; Abts, R M; Techy, G B; Miyagi, K; Shelden, C H; Rand, R W; English, L W

    1990-12-01

    We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.