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Sample records for immunotherapy major conclusions

  1. Conclusion

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Conclusion. Problems of an Under-developed Economy. Geographical Location. Terrain. Change in attitude of mainstream India required. Using Technology to overcome problems.

  2. Conclusions

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Conclusions. Be it 2G or 4G, networks are vulnerable to unwanted access and thus should be protected. 4G networks would be more sensitive as its core network will be TCP/IP based. Accordingly, resource and security management schemes with seamless ...

  3. Conclusions:

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Conclusions: Extended objects – “D-branes” – appear naturally in theories of strings. They manifest themselves as new types of physical particles in string models. They provide a powerful handle on the symmetries and dynamics of strings. Branes will play a key role ...

  4. Conclusions :

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Conclusions : No dramatic difference in the dynamics of anion-water and water-water hydrogen bonds are found for Cl- and Br- ions. Solvation shells of these ions are not rigid. For OH- in water, HB dynamics in the hydration shell determines the rate of proton transfer.

  5. Conclusions

    Indian Academy of Sciences (India)

    Microbial organisms play a major role in assimilation of P from the water column and also from the interstitial waters. Mineralisation of microbial bodies is a very rapid process and autophosphatization may occur within few hours or days after death. Geo-microbiology is an important subject and needs to be developed.

  6. Conclusion

    DEFF Research Database (Denmark)

    Sandøy, Helge; Kristiansen, Tore

    2010-01-01

    1. Comparing empirical findings with the “mountain peak model” In the introduction to this volume, we presented a “mountain peak model” of Nordic purism based on evidence showing that language scholars and lay people are very much in agreement as to where we find the more purist languages......-speaking Finland to Finnish-speaking Finland. In this conclusion to the volume, we will summarize the empirical findings presented in the volume, findings for use and attitudes alike, and compare them with the mountain peak model. That way, we may be able to estimate the nature of the cross-national ideological...

  7. 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 ...

  8. Regulatory T Cells As Supporters of Psychoimmune Resilience: Toward Immunotherapy of Major Depressive Disorder

    Science.gov (United States)

    Ellul, Pierre; Mariotti-Ferrandiz, Encarnita; Leboyer, Marion; Klatzmann, David

    2018-01-01

    There is growing evidence that inflammation plays a role in major depressive disorder (MDD). As the main role of regulatory T cells (Tregs) is to control inflammation, this might denote a Treg insufficiency in MDD. However, neither a qualitative nor a quantitative defect of Tregs has been ascertained and no causality direction between inflammation and depression has been established. Here, after reviewing the evidence supporting a relation between Treg insufficiency and MDD, we conclude that a novel therapeutic approach based on Treg stimulation could be valuable in at least the subset of patients with inflammatory MDD. Low-dose interleukin-2 appears to be a good candidate as it is not only a safe stimulator of Tregs in humans but also an inhibitor of pro-inflammatory Th17 lymphocytes. Here, we discuss that a thorough immune investigation as well as immunotherapy will be heuristic for deciphering the pathophysiology of MDD. PMID:29615964

  9. Regulatory T Cells As Supporters of Psychoimmune Resilience: Toward Immunotherapy of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Pierre Ellul

    2018-03-01

    Full Text Available There is growing evidence that inflammation plays a role in major depressive disorder (MDD. As the main role of regulatory T cells (Tregs is to control inflammation, this might denote a Treg insufficiency in MDD. However, neither a qualitative nor a quantitative defect of Tregs has been ascertained and no causality direction between inflammation and depression has been established. Here, after reviewing the evidence supporting a relation between Treg insufficiency and MDD, we conclude that a novel therapeutic approach based on Treg stimulation could be valuable in at least the subset of patients with inflammatory MDD. Low-dose interleukin-2 appears to be a good candidate as it is not only a safe stimulator of Tregs in humans but also an inhibitor of pro-inflammatory Th17 lymphocytes. Here, we discuss that a thorough immune investigation as well as immunotherapy will be heuristic for deciphering the pathophysiology of MDD.

  10. The 2015 Dietary Guidelines Advisory Committee Scientific Report: Development and Major Conclusions.

    Science.gov (United States)

    Millen, Barbara E; Abrams, Steve; Adams-Campbell, Lucile; Anderson, Cheryl Am; Brenna, J Thomas; Campbell, Wayne W; Clinton, Steven; Hu, Frank; Nelson, Miriam; Neuhouser, Marian L; Perez-Escamilla, Rafael; Siega-Riz, Anna Maria; Story, Mary; Lichtenstein, Alice H

    2016-05-01

    The Dietary Guidelines for Americans (DGA) is published every 5 y jointly by the Department of Health and Human Services (HHS) and the USDA and provides a framework for US-based food and nutrition programs, health promotion and disease prevention initiatives, and research priorities. Summarized in this report are the methods, major conclusions, and recommendations of the Scientific Report of the 2015 US Dietary Guidelines Advisory Committee (DGAC). Early in the process, the DGAC developed a conceptual model and formulated questions to examine nutritional risk and determinants and impact of dietary patterns in relation to numerous health outcomes among individuals aged ≥2 y. As detailed in the report, an expansive, transparent, and comprehensive process was used to address each question, with multiple opportunities for public input included. Consensus was reached on all DGAC's findings, including each conclusion and recommendation, and the entire report. When research questions were answered by original systematic literature reviews and/or with existing, high-quality expert reports, the quality and strength of the evidence was formally graded. The report was organized around the following 5 themes: 1) food and nutrient intakes and health: current status and trends; 2) dietary patterns, foods and nutrients, and health outcomes; 3) diet and physical activity behavior change; 4) food and physical activity environments; and 5) food sustainability and food safety. The following 3 cross-cutting topics were addressed: 1) sodium, 2) saturated fat, and 3) added sugars. Physical activity recommendations from recent expert reports were endorsed. The overall quality of the American diet was assessed to identify overconsumed and underconsumed nutrients of public health concern. Common food characteristics of healthy dietary patterns were determined. Features of effective interventions to change individual and population diet and physical activity behaviors in clinical, public

  11. Component-resolved evaluation of the content of major allergens in therapeutic extracts for specific immunotherapy of honeybee venom allergy

    DEFF Research Database (Denmark)

    Blank, Simon; Etzold, Stefanie; Darsow, Ulf

    2017-01-01

    Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant...... major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due...... to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic...

  12. The majority of patients with metastatic melanoma are not represented in pivotal phase III immunotherapy trials

    DEFF Research Database (Denmark)

    Donia, Marco; Kimper-Karl, Marie Louise; Høyer, Katrine Lundby

    2017-01-01

    BACKGROUND: Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of 'real-world' patients diag...... a huge knowledge gap regarding the usefulness of new immunotherapies in the 'real-world' patient population, and urge additional testing of known regimens in selected poor prognosis cohorts.......BACKGROUND: Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of 'real-world' patients...... in 2014, were included in the analysis. Seven pre-defined eligibility criteria, all used to select patients for enrolment in five recent randomised phase III immunotherapy trials, were analysed. RESULTS: Fifty-five percent of the total population with MM did not meet one or more eligibility criteria ('not...

  13. 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. ...

  14. 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)

  15. Consequences of major nuclear accidents on wild fauna and flora: dosimetric assessments remain a weakness to establish robust conclusions

    International Nuclear Information System (INIS)

    2014-01-01

    As about hundred of studies have been undertaken after the major nuclear accidents (Chernobyl and Fukushima) to study the consequences of these accidents on wild flora and fauna, notably on the effects of low doses of ionizing radiations, it appears that some of them reported noticeable effects due to extremely low doses. Such findings put knowledge in radiobiology into question again. This note aims at discussing the importance of the quality of dosimetric assessments for any study performed 'in natura'. It seems that the ambient external dose rate is not systematically a good indicator of the dose or dose rate absorbed by a living organism in radio-contaminated environment. This note outlines the problem related to the spatial heterogeneity of the radioactive contamination, that some statistic methods are not always adapted to data set quality. It briefly indicates other factors which may affect the quality of data set obtained during in situ studies

  16. 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, ...

  17. Sweet Conclusion

    Science.gov (United States)

    Shirley, Britt M.; Wooldridge, Barbara Ross; Camp, Kerri M.

    2012-01-01

    Jen Harrington is the owner and pastry chef of Sweet Conclusion, a bakery in Tampa, Florida. Most of Harrington's business comes from baking wedding cakes, but she has been attempting to attract customers to her retail bakery, where she sells cupcakes, pies, ice cream, and coffee. Nearly four years she opened Sweet Conclusion, the retail part of…

  18. Conclusion; Zaklyuchenie

    Energy Technology Data Exchange (ETDEWEB)

    Nikitin, V I

    1961-07-01

    In this chapter of book are present conclusions about work done by author, in particular that he found comparatively simple and available ways of synthesis of glycerin of acetylene line and glycerin of ethylen line which before was unknown or almost unknown in the chemical literature.

  19. General conclusions

    International Nuclear Information System (INIS)

    Tubiana, M.

    1993-01-01

    In conclusion, a general consensus of a number of points which the author endeavours to summarize in this article: -doctors are an excellent channel for passing on information to the public -doctors feel that they do not know enough about the subject and a training on radiobiology and radiation protection is a necessity for them -communication between doctors and the general public is poor in this field -research should be encouraged in numerous areas such as: carcinogenic effect of low doses of radiation, pedagogy and risk perception

  20. 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....

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Impact of allergen immunotherapy after two years of suspension in patients with asthma

    Directory of Open Access Journals (Sweden)

    Jorge Sánchez

    2016-05-01

    Conclusion: The allergen immunotherapy improves asthma control and reduces the required doses of pharmacotherapy. These effects have an important impact on quality of life and perhaps economically for patients with asthma. The beginning at an early age seems to have a major impact.

  8. 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.

  9. 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

  10. Mutants of the major ryegrass pollen allergen, Lol p 5, with reduced IgE-binding capacity: candidates for grass pollen-specific immunotherapy.

    Science.gov (United States)

    Swoboda, Ines; De Weerd, Nicole; Bhalla, Prem L; Niederberger, Verena; Sperr, W R; Valent, Peter; Kahlert, Helga; Fiebig, Helmut; Verdino, Petra; Keller, Walter; Ebner, Christof; Spitzauer, Susanne; Valenta, Rudolf; Singh, Mohan B

    2002-01-01

    More than 400 million individuals are sensitized to grass pollen allergens. Group 5 allergens represent the most potent grass pollen allergens recognized by more than 80 % of grass pollen allergic patients. The aim of our study was to reduce the allergenic activity of group 5 allergens for specific immunotherapy of grass pollen allergy. Based on B- and T-cell epitope mapping studies and on sequence comparison of group 5 allergens from different grasses, point mutations were introduced by site-directed mutagenesis in highly conserved sequence domains of Lol p 5, the group 5 allergen from ryegrass. We obtained Lol p 5 mutants with low IgE-binding capacity and reduced allergenic activity as determined by basophil histamine release and by skin prick testing in allergic patients. Circular dichroism analysis showed that these mutants exhibited an overall structural fold similar to the recombinant Lol p 5 wild-type allergen. In addition, Lol p 5 mutants retained the ability to induce proliferation of group 5 allergen-specific T cell lines and clones. Our results demonstrate that a few point mutations in the Lol p 5 sequence yield mutants with reduced allergenic activity that represent potential vaccine candidates for immunotherapy of grass pollen allergy.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Specific IgG and its subclass antibodies after immunotherapy with gynandropsis gynandra

    Directory of Open Access Journals (Sweden)

    Latha G

    2005-01-01

    Full Text Available Background : About 10 to 15 % of the Indian population is known to suffer from major allergic disorders such as Asthma, Rhinitis, Atopic Dermatitis and Urticaria. Aeroallergens play a major role in the pathogenesis of respiratory allergic diseases. Among the aeroallergens, pollens are major causative agents. The predominance of pollen allergens necessitate the need to assess the specific immunotherapy (SIT in allergic patients. Objective : To evaluate the effect of immunotherapy based on the presence of IgG and its subclass antibodies towards whole pollen antigen of Gynandropsis gynandra (G.gynandra and its fractions. Material and Methods : A study was conducted in 30 bronchial asthma patients on immunotherapy, by assessing the levels of IgG and its subclasses specific to G. gynandra pollen. Results : There was a significant increase in IgG and its subclass antibodies to whole pollen antigen and its fractions i.e.> 90kD, 46-37kD and 36-32kD after the course of IT. Conclusion : The use of peptide fractions may be more appropriate instead of the whole pollen antigen to test the effect of immunotherapy.

  16. IgE and allergen-specific immunotherapy-induced IgG4 recognize similar epitopes of Bet v 1, the major allergen of birch pollen.

    Science.gov (United States)

    Groh, N; von Loetzen, C S; Subbarayal, B; Möbs, C; Vogel, L; Hoffmann, A; Fötisch, K; Koutsouridou, A; Randow, S; Völker, E; Seutter von Loetzen, A; Rösch, P; Vieths, S; Pfützner, W; Bohle, B; Schiller, D

    2017-05-01

    Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G 4 which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG 4 specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG 4 antibodies are developed is under debate. We sought to analyze the epitope specificities of IgE and IgG 4 antibodies from sera of patients who received AIT. 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG 4 were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a _11x , modified in five potential epitopes, were analyzed by circular dichroism and nuclear magnetic resonance spectroscopy. IgE binding to Bet v 1 was assessed by ELISA and mediator release assays. Competitive binding of monoclonal antibodies specific for Bet v 1a and serum IgE/IgG 4 to rBet v 1a and serum antibody binding to a non-allergenic Bet v 1-type model protein presenting an individual epitope for IgE was analyzed in ELISA and western blot. rBet v 1a _11x had a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a _11x was concentration and buffer-dependent. Up to 1500-fold increase in the EC 50 for IgE-mediated mediator release induced by rBet v 1a _11x was determined. The reduction of IgE and IgG 4 binding to rBet v 1a _11x was comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG 4 to 66.1% and 64.9%, respectively. Serum IgE and IgG 4 bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera. Patients receiving AIT develop Bet v 1a-specific IgG 4 which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG 4 might stimulate the development of epitope-specific diagnostics and therapeutics. © 2016 John Wiley & Sons Ltd.

  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. 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.

  20. Summary and conclusions [Chapter 11

    Science.gov (United States)

    Daniel G. Neary; John N. Rinne; Alvin L.. Medina

    2012-01-01

    Summaries and conclusions of each chapter are compiled here to provide a “Quick Reference” guide of major results and recommendations for the UVR. More detail can be obtained from individual chapters.

  1. 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...

  2. 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. ...

  3. 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

  4. 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.

  5. 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....

  6. 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.

  7. Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom

    Science.gov (United States)

    2013-01-01

    Background Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms “double sensitization” or “double positivity” cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients. Objective We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients. Methods Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests. Results Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15). Conclusions Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the

  8. 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.

  9. 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...

  10. General conclusions on workshop

    International Nuclear Information System (INIS)

    Rustand, H.

    2006-01-01

    The author proposes a general conclusion on the second workshop on the indemnification of damage in the event of a nuclear accident, organized in Bratislava, the 18-20 May 2005. He pointed out the most important discussions and the results revealed during these two days. (A.L.B.)

  11. 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.

  12. Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence

    Directory of Open Access Journals (Sweden)

    Ridnour Lisa A

    2011-09-01

    Full Text Available Abstract Background Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s by which they occur. Methods We have examined the matrix metalloproteinase (MMP protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which we examined 22 month old APPSw mice that had received anti-Aβ antibodies for 1, 2 or 3 months. The second is an active vaccination study in which we examined 16 month old APPSw/NOS2-/- mice treated with Aβ vaccination for 4 months. Results There is a significant activation of the MMP2 and MMP9 proteinase degradation systems by anti-Aβ immunotherapy, regardless of whether this is delivered through active vaccination or passive immunization. We have characterized this activation by gene expression, protein expression and zymography assessment of MMP activity. Conclusions Since the MMP2 and MMP9 systems are heavily implicated in the pathophysiology of intracerbral hemorrhage, these data may provide a potential mechanism of microhemorrhage due to immunotherapy. Increased activity of the MMP system, therefore, is likely to be a major factor in increased microhemorrhage occurrence.

  13. Conclusions and recommendations

    International Nuclear Information System (INIS)

    1984-01-01

    The FAO/IAEA/GSF/SIDA Co-ordinated Research Programme on Cereal Grain Protein Improvement by Nuclear Techniques was a follow-up to the FAO/IAEA/GSF Co-ordinated Research Programme on the Use of Nuclear Techniques for Seed Protein Improvement. It was initiated in 1969 and ended in 1981. The objectives of the meeting were to review and evaluate the achievements of the current and previous programmes in order to draw conclusions on the possibility of genetic improvement of cereal grain protein using nuclear techniques, to identify unsolved problems and to discuss and propose possible approaches for their solution. Through reviews and discussions, conclusions and recommendations were made by the participants

  14. 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.

  15. 7. Conclusions and reflections

    OpenAIRE

    Nettle, Daniel

    2016-01-01

    But now your eyes sing the sad, sad song,Of how you lived so fast and died so young. Introduction We’ve now finished the data chapters of this book, and some conclusions are in order. In this chapter, I summarise what strike me as the main things we have learned, and suggest what their implications might be. I then devote a more extended discussion to the issue of causes of patterns of social behaviour, and how our data might bear on it. From this follows a brief consideration of what kinds o...

  16. Conclusions and recommendations

    International Nuclear Information System (INIS)

    Carrette, M.

    1997-01-01

    The paper presents conclusions and recommendations at the closing session of the NEA/OECD Workshop held at Fontenay-aux-Roses on 12-14 June 1995. The conclusions refer to issues like: public reaction to foodstuffs containing radioisotope concentrations under the danger standards, possible non-adherence of manufacturers, processors, distributors, et al, to the instructions and guidance from radiation protection specialists, integration of all the food chain factors in the elaboration of the emergency intervention programs, etc. Among the most significant recommendations the following may be mentioned: 1. Differences between different intervention levels and the maximum admissible levels agreed upon by national, regional or international nutrition authorities should be further studied; 2. Problems created by the Chernobyl accident (as for instance, the methods of treatment of food chain products containing unacceptable radioactivity concentrations) are still present and must be solved; 3. Further studies should be done on the socio-cultural aspects of the communication, particularly on the information in rural environment; 4. The preventive measures in agriculture should be implemented as rapidly as possible; 5. In elaborating programmes of agriculture countermeasures, the management of contaminated media, particularly, of forests and their effect on agriculture

  17. 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.

  18. 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.

  19. Summary and conclusions

    International Nuclear Information System (INIS)

    2000-01-01

    The international workshop on 'Nuclear Power Plant Life Management in a Changing Business World' was held in Washington, DC, on 26-27 June 2000. This workshop was attended by more than 50 experts from 12 countries and three international organisations. The workshop included a series of presentations to a plenary session of all participants. A spectrum of experiences in plant life extension activities as well as experiences in operating a nuclear power plant (NPP) in a 'free-market' electricity environment were presented: The workshop also included three working groups in which major issues facing PLIM activities for NPPs were identified and discussed. The three working groups covered technology, regulation and business. The following sections of this report consist of summaries of the discussions that took place in each of the three working groups. (author)

  20. Summary and Conclusions

    International Nuclear Information System (INIS)

    2013-01-01

    This section summarizes the presentations and Panel discussions of the 4 technical sessions of the workshop: 1 - Regulatory cooperation on generic and design specific issues, MDEP working groups (EPR, AP1000), vendor inspection co-operation, digital I and C, and codes and standards (7 presentations); 2 - Regulatory positions on siting practices and enhancements as a result of lessons learned from Fukushima accident (5 presentations); 3 - Construction experience and regulatory oversight of new reactor construction activities (6 presentations); 4 - Lessons learned from regulatory licensing reviews of new reactor designs (6 presentations). The main workshop conclusions are listed as follows: - Harmonization is a long term goal and significant progress has been made. However, this long term objective needs to be associated with short term measurable steps; - MDEP approach to tackle on one side with specific technical subjects, and to strive harmonisation on generic topics was considered appropriate; - Convergence on technical requirements is more realistic than harmonization of codes and standard; - Beneficial early engagement of different stakeholders specially at the siting stage has been acknowledged; - Need to characterise the hazards and to keep updated the safety assessment (PSR); - Land use issues are important particularly after Fukushima; - Commissioning aspects (e.g. training aspects for inspectors) should be addressed by WGRNR taking into account MDEP interaction; - Importance of WGRNR ConEx Programme: construction experience sharing is a leverage for quality and so for a future safe operation of NPPs; - Capability of licensee to follow the responsibility of design changes (could be an issue for small utilities); - Importance of Periodic Safety Reviews to review and account for the design. Finally, the WGRNR has convened that a third conference should be held in about two years time (2014- 2015)

  1. Summary and conclusions

    International Nuclear Information System (INIS)

    2011-01-01

    authorities, reactor designers, and operators/ licensees perspectives on the various practices used in the regulation of nuclear power plant siting (selection, evaluation and site preparation). This session was also aimed to address issues on sites where a mixture of activities are taking place (e.g., operating units, new construction, decommissioning, etc.) including organisation of the regulators and licensee/engineering organisation, methods, systems, etc. Conclusions: In general workshop participants agreed on the need to regularly have these kind of forums to discuss relevant regulatory issues for new builds. One important aspect of this workshop was the participation of 'New Entrants'. The interaction between NEA member countries with mature nuclear power plants and newcomers was quite important since it gave newcomers the possibility to benefit of mature international practices in order to focus their regulatory oversight and control. NEA members could also benefit from insights the New Entrants discover as they develop or enhance their regulatory controls. In addition technical exchanges associated with construction experience of New Entrants as they begin to license, build and operate NPP could benefit NEA members

  2. 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.

  3. Conclusions

    Indian Academy of Sciences (India)

    In long-term better adapted varieties are needed to adapt to multiple stresses linked with climate change. ... and water management are available which can help minimize negative impacts. ... Adaptation practices take time to become effective.

  4. Conclusion

    NARCIS (Netherlands)

    Grignon, F.; Mazrui, A.; Rutten, M.M.E.M.; Rutten, M.M.E.M.; Mazrui, A.; Grignon, F.

    2001-01-01

    The outcome of a three-day conference held at the African Studies Centre, Leiden, The Netherlands, in September 1998, this book on the 1997 Kenya general elections is organized in four parts: the direct pre-electoral background; technical and national analysis of the general elections, including the

  5. Conclusion

    OpenAIRE

    Rainhorn, Jean-Daniel; Boudamoussi, Samira El

    2017-01-01

    “Science without conscience is but the ruin of the soul.”—François Rabelais, 1542 A special feature of this book is to bring together the work of researchers coming from different disciplines and having various themes of reflection or practices in the field of biomedicine. While the general trend of science goes towards increasing specialization, the project of this book is to look at the use of medical advances in a transversal perspective. In other words, it intends to highlight what unregu...

  6. Conclusions

    International Nuclear Information System (INIS)

    Mandil, C.

    1994-01-01

    The renewable energies and the nuclear one are complementary. They belong to the french energy policy, which has three aims: strategic, economic and environmental. They contribute to the diversification of the energy balance and to the energy competitiveness. Energy savings might be achieved and renewable energies might be developed for the future

  7. Conclusions

    Indian Academy of Sciences (India)

    Confounding effect of obesity and associated co-morbidities (especially on metabolic abnormalities, cardiovascular and cerebrovascular morbidity) should be clearly dissected out in future studies ...

  8. Conclusion

    OpenAIRE

    Houmed Soulé, Aramis

    2018-01-01

    Au cours de son règne qui a duré plus d’une quarantaine d’années, en une période cruciale de l’histoire de la Corne de l’Afrique, Maḥammad Ḥanfaré parvient à préserver son sultanat, à défaut de l’ensemble du pays ‘Afar, des visées impérialistes d’où qu’elles viennent. Malheureusement, l’indépendance de cette entité politique ‘Afar ne lui survit pas, du moins sur le plan international. Des luttes fratricides pour sa succession qui opposent ses nombreux héritiers et dont les prémices apparaisse...

  9. Conclusion

    DEFF Research Database (Denmark)

    Fahnøe, Kristian Relsted; Warming, Hanne

    2017-01-01

    analysis approach reveal how clients’ struggles in intimate and societal life, and in public and private spaces, are intertwined with geo-politics and global flows of governance strategies, e.g. neoliberalism and managerialism, which also condition social work practices. Indeed, social work constitutes......Fahnøe and Warming provide a cogent overview of how a lived citizenship approach enables critical analyses of social work and social policies by addressing challenges related to rights, recognition, participation, belonging and identity. The sub-concept of intimate citizenship and a spatial...... a kind of sociological magnifying glass through which broader social changes can be studied, including dynamics of inclusion and exclusion, new conflicts and modes of resistance, and new social pathologies....

  10. Conclusion

    DEFF Research Database (Denmark)

    Warming, Hanne; Fahnøe, Kristian

    2017-01-01

    analysis approach reveal how clients’ struggles in intimate and societal life, and in public and private spaces, are intertwined with geo-politics and global flows of governance strategies, e.g. neoliberalism and managerialism, which also condition social work practices. Indeed, social work constitutes......Warming and Fahnøe provide a cogent overview of how a lived citizenship approach enables critical analyses of social work and social policies by addressing challenges related to rights, recognition, participation, belonging and identity. The sub-concept of intimate citizenship and a spatial...... a kind of sociological magnifying glass through which broader social changes can be studied, including dynamics of inclusion and exclusion, new conflicts and modes of resistance, and new social pathologies....

  11. Conclusion

    DEFF Research Database (Denmark)

    de Vreese, Claes; Reinemann, Carsten; Esser, Frank

    2017-01-01

    At the outset, we asked if there is any good news about the news and, if so, where the good news is. In academic research and public discussions about news and democracy, one fi nds different interpretations of the state of current news provision. A tendency towards pessimism about current news...... is seen as having a negative impact on the quality of political life and democracy. Set against the pessimism and caution in the public debate and literature on news quality and the performance of political journalism, we were not optimistic that we would fi nd good-quality news or that we would be able...... to offer some good news as a positive antidote, so to speak, to the pervasive pessimism in the literature....

  12. Conclusions

    International Nuclear Information System (INIS)

    Brookes, L.G.; Motamen, H.

    1984-01-01

    The paper covers the following: economics of nuclear power; nuclear or fossil-fuel plants; power systems; methods of capital investment appraisal; size factor; nuclear industry; uranium demand; fuel cycle; fast reactors; choice of reactors; case studies from France; power plants in USA and West Germany; electricity tariffs; nuclear energy in Middle Eastern states; energy growth and economic growth; nuclear energy as macroeconomic influence; future energy options. (U.K.)

  13. Conclusion

    DEFF Research Database (Denmark)

    Jørgensen, Christian Helms; Wallo, Andreas; Toiviainen, Hanna

    2015-01-01

    Work in times of globalisation and uncertainty is undergoing considerable changes, which has strengthened the importance of work as a site of learning. New trends in production, such as digitalisation, challenge traditional modes of producing goods and services. Emerging forms of flexible...... production and knowledge-work offer growing learning opportunities to people throughout their active working life. In contrast to the stable and standardised modes of Fordist production, modern working life is characterised by rapid changes and employees interacting across globally distributed professional...... explores the challenges of working and learning on the boundaries between education and working life. Globalisation affects the transition patterns from vocational education to the labour market in many ways (Schoon & Silbereisen, 2009), even though the specific challenges to national-level policies vary...

  14. Conclusions

    Science.gov (United States)

    Ahonen, Pasi; Alahuhta, Petteri; Daskala, Barbara; Delaitre, Sabine; Hert, Paul De; Lindner, Ralf; Maghiros, Ioannis; Moscibroda, Anna; Schreurs, Wim; Verlinden, Michiel

    Some say that an increase in security does not necessarily mean a further encroachment on privacy - indeed, security is necessary to protect personal data and our privacy. Networks must be secure, our personal devices, reliable, dependable and trustworthy. But security is a multifaceted term, with many dimensions. We are of the view that an increase in security most likely will encroach upon our privacy in an ambient intelligence world. Surveillance cameras will continue to proliferate. We assume that, whatever the law is, whatever privacy protections government and business say they honour, our telecommunications, e-mails and Internet usage will be monitored to an increasing degree. The same will be true of our interfaces with the world of ambient intelligence.

  15. Conclusion

    International Nuclear Information System (INIS)

    Ainul Hayati Daud; Hazmimi Kasim

    2010-01-01

    In Asia, Japan and the Republic of Korea have conducted similar studies but relying on statistical data and used inputs and outputs (I-O) methodology, utilizing on general macro-level data. In contrast, this study captures data directly through surveys using questionnaires, face-to-face interviews, case studies and focus group discussions. The impact of nuclear technology applications in Malaysia were evaluated both quantitatively and qualitatively. These impacts are then linked to a broader objective associated with technological development, namely wealth generation, knowledge generation and societal well-being. In the process of the study, users and practitioners of the technology highlighted issues and challenges faced by them. To cap the study, the level of activities of nuclear technology in Malaysia was benchmarked against those in Japan and the Republic of Korea. This chapter highlights the results of the study, the outcome of the study, followed by recommendations as response to issues and challenges raised by respondents, and finally the way forward for monitoring and charting further progress of nuclear technology in the country. (author)

  16. Conclusions

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. First study on fHSC. First study on fHSC. fHSC exhibit embryonic stem cell like properties. fHSC therapy results in myocardial regeneration in rat model of MI. fHSC may be a novel stem cell type for cardiovascular regeneration.

  17. Conclusion

    International Nuclear Information System (INIS)

    2000-01-01

    In the monograph peculiarities of radioinduced sexual dysfunctions of Chernobyl accident liquidators are described. It is shown, that ones of principal clinical manifestations of stochastic radio-genetic effects are sexual dysfunctions. Assessment in point of view of stages and components of copulative cycle is carried out. Authors made attempt to take in account all involved in sexual dysfunctions systems for examined contingent. It is noted, that genesis of radioinduced sexual dysfunctions is complex and it includes both the influence of vegetative nervous system damage and the direct damage of gonads. During clinical examination with patients it is revealed that both vegetative-vascular dysfunctions and asteno-neurotic dysfunctions are dominating. Authors noting that mentioned sexual dysfunctions are caused by low dose irradiation, and they have certain distinctions. Measures for comprehensive rehabilitation of suffered contingent in late period after irradiation are developed

  18. Conclusion

    International Nuclear Information System (INIS)

    Timofeev, Yu.M.; Zikiryakhodjaev, D.Z.

    1997-01-01

    In this chapter of book authors made following summary: the cancerous growths of anal canal is rare form of growths; extension of anal canal depends from sex, age, weight and growth of patient; the developed schemes of classification and staging of cancerous growths of anal canal have important role for growths systematization; typical symptoms are blood in excrement, pains in anus, presence of swelling in anus, the treatment of the cancerous growths of anal canal must be varied

  19. 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...

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Specific IgE response to different grass pollen allergen components in children undergoing sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    Marcucci Francesco

    2012-06-01

    Full Text Available Abstract Background Grass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized. Methods We investigated in 30 children (19 males and 11 females, mean age 11.3 years, 19 treated with sublingual immunotherapy (SLIT by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components. Results Significant increases (p  Conclusions These findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Immunotherapy: A breakthrough in cancer research

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2016-12-01

    test the effectiveness of the tuberculosis vaccine Bacille Calmette-Guérin (BCG in treating superficial bladder cancer. The BCG treatment, in which BCG bacilli are inserted directly into a patient’s bladder via a catheter, proved to be an effective form of immunotherapy and the groundbreaking technique is still used today. In general, studies on immunotherapy have presented researchers with two important conclusions: First and foremost, researchers were finally able to prove that the immune system is indeed capable of recognizing cancer cells as a ‘foreign entity’ although they originate from the body’s own tissues. Secondly, by boosting the immune response, researchers are able to enhance other cancer-killing agents at the same time, thus increasing the chances of a successful treatment via immunotherapy. Based on these conclusions, researchers all over the world now face the challenge of figuring out which therapy works best for a specific type of cancer and why some cancer patients respond better than others to the prescribed treatments.At the ESMO Asia 2016 congress, lead author Dr. Makoto Tahara presented his paper ‘Asian head and neck cancer patients live longer with immunotherapy than mixed race group’, in which his team of researchers reported the sub-analysis results on the safety and efficacy of pembrolizumab in 26 patients (of Asian Pacific origin who received a fixed dose of the humanized antibody for 24 months until the detection of disease progression or adverse events. They observed that both the median overall survival and the disease control rate were better in Asians than the overall population, i.e. 11.5 versus 8.4 months and 50.5% versus 37.9%, respectively.According to Dr. Tahara, “The fixed dose of pembrolizumab was well-tolerated in Asian Pacific patients with recurrent/metastatic head and neck cancer. Although the Asian population was small, our findings suggest that they have better median overall survival with pembrolizumab than

  14. 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

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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 ...

  2. 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....

  3. 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.

  4. 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.

  5. Northern Canada in a Changing Climate: Major Findings and Conclusions

    Energy Technology Data Exchange (ETDEWEB)

    Prowse, Terry D.; Peters, Daniel L. (Water and Climate Impacts Research Centre, Environment Canada, Dept. of Geography, Univ. of Victoria, Victoria, BC (Canada)). e-mail: terry.prowse@ec.gc.caa; Furgal, Chris (Indigenous Environmental Studies Program, Trent Univ., Peterborough, ON (Canada))

    2009-07-15

    Key findings include: Climate-induced changes in the cryosphere have large implications for infrastructure maintenance and design. Much of the infra-structure in the North is dependent upon the cryosphere to, for example, provide stable surfaces for buildings and pipelines, contain wastes, stabilize shorelines, and provide access to remote communities in the winter. Permafrost warming and thaw may require remedial action or further engineering modifications to existing infrastructure. Waste retention ponds and lakes that rely on the impervious nature of permafrost to retain environmentally hazardous materials are a particular concern. In the longer term, marine and freshwater transportation will need to shift its reliance from ice routes to open-water or land-based transport systems. Coastal areas and communities will also become more vulnerable to erosion with loss of sea ice compounded with increased storminess and rising sea levels. Changes in the timing of river flows will require modifications to the infrastructure and flow strategies used in generating hydroelectricity. As the climate continues to change, there will be consequences for biodiversity shifts and in ranges and distribution of many species with impacts on availability, accessibility, and quality of resources upon which human populations rely. The northward migration of species, and disruption and competition from invading species, are already occurring and will continue to alter terrestrial and aquatic communities. Shifting environmental conditions will likely introduce new animal transmitted diseases and redistribute some existing diseases, affecting key economic resources and some human populations. Stress on populations of iconic wildlife species will likely continue as a result of changes to critical sea-ice habitat. Where these stresses affect economically or culturally important species, they will have significant impacts on people and regional economies. Increased navigability of Arctic marine waters and expansion of land- and fresh water-based transportation networks will lead to a less 'remote' northern Canada, bringing both opportunities for growth in a range of economic sectors, and challenges associated with culture, security, and the environment. Diminishing sea ice, particularly in Hudson Bay and the Beaufort Sea, and a lengthened summertime shipping season associated with warming, will increase opportunities for shipping and passage within Canadian Arctic waters. Loss of sea and fresh ice will also likely lead to the development of marine ports and all-season road networks to interior portions of the northern mainland and Arctic islands, particularly to access natural resources whose development has previously been unesco-nomical. Socioeconomic and cultural impacts on Arctic communities from increased economic activity, including increased marine traffic, and access associated with the opening of the Northwest Passage may be far reaching. While maintaining and protecting aspects of traditional and subsistence ways of life in many Arctic Aboriginal communities may become more difficult in a changing climate, new opportunities will also be presented

  6. 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.

  7. 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.

  8. Immunotherapy for Urothelial Carcinoma: Current Status and Perspectives

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. 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

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Budget impact analysis of two immunotherapy products for treatment of grass pollen-induced allergic rhinoconjunctivitis

    Directory of Open Access Journals (Sweden)

    Rønborg SM

    2012-09-01

    Full Text Available Steen M Rønborg,1 Ulrik G Svendsen,2 Jesper S Micheelsen,3 Lars Ytte,4 Jakob N Andreasen,5 Lars Ehlers61The Pulmonology and Allergy Clinic of Copenhagen, Copenhagen, 2Bispebjerg Hospital, Copenhagen, 3Private ENT practice, Aalborg, 4General Practice Aalborg, 5ALK, Hørsholm, 6Aalborg University, Aalborg, DenmarkBackground: Grass pollen-induced allergic rhinoconjunctivitis constitutes a large burden for society. Up to 20% of European and United States (US populations suffer from respiratory allergies, including grass pollen-induced allergic rhinoconjunctivitis. The majority of patients are treated with symptomatic medications; however, a large proportion remains uncontrolled despite use of such treatments. Specific immunotherapy is the only treatment documented to target the underlying cause of the disease, leading to a sustained effect after completion of treatment. The aim of this study was to compare the economic consequences of treating patients suffering from allergic rhinoconjunctivitis with either a grass allergy immunotherapy tablet (AIT or subcutaneous immunotherapy (SCIT.Methods: A budget impact analysis was applied comparing SQ-standardized grass AIT (Grazax®; Phleum pratense, 75,000 SQ-T/2,800 BAU; ALK, Denmark with SCIT (Alutard®; P. pratense, 100,000 SQ-U/mL; ALK, Denmark. Budget impact analysis included health care utilization measured in physical units based on systematic literature reviews, guidelines, and expert opinions, as well as valuation in unit costs based on drug tariffs, physician fees, and wage statistics. Budget impact analysis was conducted from a Danish health care perspective.Results: Treating patients suffering from allergic rhinoconjunctivitis with grass AIT instead of grass SCIT resulted in a total reduction in treatment costs of €1291 per patient during a treatment course. This cost saving implies that approximately 40% more patients could be treated with grass AIT per year without influencing the cost of

  16. CONCLUSIONS Urban Children and Adolescents

    Indian Academy of Sciences (India)

    CONCLUSIONS Urban Children and Adolescents. Increasing prevalence of overweight and obesity and measures of regional (central) adiposity. High prevalence of markers of dysmetabolic state in urban adolescents. ~10% prevalence of dysglycemia in overweight / obese school children.

  17. Chapter 6: Conclusions and recommendations

    International Nuclear Information System (INIS)

    1995-01-01

    This chapter provides a brief summary of conclusions with respect to project implementation issues. Furthermore, the chapter contains recommendations on future applications of the modelling system and on water resources management in the project area

  18. 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...

  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. 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

  3. CONCLUSIONS New Delhi Birth Cohort

    Indian Academy of Sciences (India)

    CONCLUSIONS New Delhi Birth Cohort. Crossing BMI centiles and early adiposity rebound associated with adult metabolic syndrome. BMI gain in infancy and early childhood – associated more with adult lean mass. BMI gain in later childhood / adolescence – associated more with adult fat mass and constituents of ...

  4. 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...

  5. 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

  6. 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...

  7. [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).

  8. 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.

  9. 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.

  10. 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.

  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. 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...

  13. 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....

  14. 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).

  15. 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.

  16. 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.

  17. 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)

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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...

  5. 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.

  6. Dendritic cells used in anti-HIV immunotherapy showed different modulation in anti-HIV genes expression: New concept for the improvement of patients' selection criteria

    Directory of Open Access Journals (Sweden)

    Alessandra Pontillo

    2016-11-01

    Conclusions: These results suggest that the actual selection of HIV+ individual for immunotherapy, based on clinical features, did not ensure the same DC product, and that less “activated/exhausted” DC could positively affect the outcome of immunotherapy.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. [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.

  18. 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...

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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)

  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. 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)

  10. 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.

  11. 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...

  12. A prospective highlight on exosomal nanoshuttles and cancer immunotherapy and vaccination

    Directory of Open Access Journals (Sweden)

    Mohammad A. Rafi

    2015-08-01

    Conclusions: As complex systems, these vesicular micro-/nano-machines convey important cellular messages dependent upon the cells/tissue setting(s. In addition to their potential in diagnosis of cancers, they have been exploited for cancer immunotherapy/vaccination. However, such treatment strategies need to be carefully designed to attain desired clinical outcomes.

  13. Addressing current challenges in cancer immunotherapy with mathematical and computational modelling.

    Science.gov (United States)

    Konstorum, Anna; Vella, Anthony T; Adler, Adam J; Laubenbacher, Reinhard C

    2017-06-01

    The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development. © 2017 The Author(s).

  14. Computational prediction of vaccine potential epitopes and 3-dimensional structure of XAGE-1b for non-small cell lung cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Mohammad M. Tarek

    2018-04-01

    Conclusions: This study predicted a model of XAGE-1b tertiary structure which could explain its antigenic function and facilitate usage of predicted peptides for experimental validation towards designing immunotherapies against NSCLC.

  15. Efficacy of oral immunotherapy with a rice-based edible vaccine containing hypoallergenic Japanese cedar pollen allergens for treatment of established allergic conjunctivitis in mice

    Directory of Open Access Journals (Sweden)

    Ken Fukuda

    2018-01-01

    Conclusions: Oral administration of transgenic rice seeds expressing hypoallergenic allergens ameliorated allergic conjunctivitis in the established setting. Such a rice-based edible vaccine is potentially both safe and effective for oral immunotherapy in individuals with allergic conjunctivitis.

  16. Gene expression analysis in predicting the effectiveness of insect venom immunotherapy

    NARCIS (Netherlands)

    Niedoszytko, M.; Bruinenberg, M.; de Monchy, J.; Wijmenga, C.; Platteel, M.; Jassem, E.; Oude Elberink, Joanna N.G.

    Background: Venom immunotherapy (VIT) enables longtime prevention of insect venom allergy in the majority of patients. However, in some, the risk of a resystemic reaction increases after completion of treatment. No reliable factors predicting individual lack of efficacy of VIT are currently

  17. Retrospective Comparative Study of the Effects of Dendritic Cell Vaccine and Cytokine-Induced Killer Cell Immunotherapy with that of Chemotherapy Alone and in Combination for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jingxiu Niu

    2014-01-01

    Full Text Available Purpose. This retrospective study determined the delayed-type hypersensitivity (DTH skin test and safety of dendritic cell (DC vaccine and cytokine-induced killer (CIK cell immunotherapy and the survival compared to chemotherapy in 239 colorectal cancer (CRC patients. Methods. DTH and safety of the immunotherapy were recorded. The overall survival (OS and disease free survival curves were compared according to the immunotherapy and/or chemotherapy received with Kaplan-Meier estimates. Results. Of the 70 patients who received immunotherapy, 62.86% had a positive DTH skin test, 38.57% developed fever, 47.14% developed insomnia, 38.57% developed anorexia, 4.29% developed joint soreness, and 11.43% developed skin rash. For 204 resectable CRC patients, median survival time (MST (198.00 days was significantly longer in patients with immunotherapy plus chemotherapy than with chemotherapy alone (106.00 days (P=0.02. For 35 patients with unresectable or postsurgery relapsed CRC and who were confirmed to be dead, no statistical difference was observed in the MST between the patients treated with immunotherapy and with chemotherapy (P=0.41. MST in the patients treated with chemotherapy plus immunotherapy was 154 days longer than that of patients treated with chemotherapy alone (P=0.41. Conclusions. DC vaccination and CIK immunotherapy did not cause severe adverse effects, induce immune response against CRC, and prolong OS.

  18. 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

  19. 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.

  20. [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.

  1. 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...

  2. 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.

  3. Association between competing interests and authors' conclusions

    DEFF Research Database (Denmark)

    Kjaergard, Lise L; Als-Nielsen, Bodil

    2002-01-01

    To assess the association between competing interests and authors' conclusions in randomised clinical trials.......To assess the association between competing interests and authors' conclusions in randomised clinical trials....

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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....

  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. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

    DEFF Research Database (Denmark)

    Becker, Juergen C.; Stang, Andreas; zur Hausen, Axel

    2018-01-01

    Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations...... knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC....

  17. Global Advisory Group: conclusions and recommendations.

    Science.gov (United States)

    1986-02-01

    The conclusions and recommendations formulated for the global program by the 8th meeting of the Expanded Program on Immunization (EPI) Global Advisory Group, which took place during November 1985, are summarized. The Global Advisory Group recommends that, in furtherance of the Five-Point Action Program endorsed by the World Health Assembly in 1983, 3 general and 4 specific actions be taken by national immunization programs with the support of the World Health Organization (WHO) to accelerate EPI progress. These recommendations reflect optimism that the 1990 goal of reducing morbidity and mortality by providing immunization for all children of the world can be realized but also acknowledge that many fundamental problems of national program management remain to be resolved. The general actions are: to promote the achievement of the 1990 immunization goal at national and international levels through collaboration among ministries, organizations, and individuals in both the public and private sectors; to adopt a mix of complementary strategies for program acceleration; and to ensure that rapid increases in coverage can be sustained through mechanisms which strengthen th delivery of other primary health care interventions. The specific actions are as follows: to provide immunization at every contact point; to reduce dropout rates between 1st and last immunizations; to improve immunization services to the disadvantaged in urban areas; and to increase priority for the control of measles, poliomyelitis, and neonatal tetanus. The WHO and the UN International Children's Emergency Fund (UNICEF) have collaborated in support of the EPI since the early days of the program. The acceleration of national efforts heightens the importance of this collaboration, particularly at the national level. It may be further facilitated by the provision of policy guidance from global and regional levels, by WHO and UNICEF collaborative agreements at the regional level, and by country agreements

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies

    Directory of Open Access Journals (Sweden)

    Marco Ruella

    2016-01-01

    Full Text Available Immunotherapy is the revolution in cancer treatment of this last decade. Among multiple approaches able to harness the power of the immune system against cancer, T cell based immunotherapies represent one of the most successful examples. In particular, biotechnological engineering of protein structures, like the T cell receptor or the immunoglobulins, allowed the generation of synthetic peptides like chimeric antigen receptors and bispecific antibodies that are able to redirect non-tumor specific T cells to recognize and kill leukemic cells. The anti-CD19/CD3 bispecific antibody blinatumomab and anti-CD19 chimeric antigen receptor T cells (CART19 have produced deep responses in patients with relapsed and refractory B-cell acute leukemias. However, although the majority of these patients responds to anti-CD19 immunotherapy, a subset of them still relapses. Interestingly, a novel family of leukemia escape mechanisms has been described, all characterized by the apparent loss of CD19 on the surface of leukemic blasts. This extraordinary finding demonstrates the potent selective pressure of CART19/blinatumomab that drives extreme and specific escape strategies by leukemic blasts. Patients with CD19-negative relapsed leukemia have very poor prognosis and novel approaches to treat and ideally prevent antigen-loss are direly needed. In this review we discuss the incidence, mechanisms and therapeutic approaches for CD19-negative leukemia relapses occuring after CD19-directed T cell immunotherapies and present our future perspective.

  13. Society for immunotherapy of cancer (SITC) statement on the proposed changes to the common rule.

    Science.gov (United States)

    Kaufman, Howard L; Butterfield, Lisa H; Coulie, Pierre G; Demaria, Sandra; Ferris, Robert L; Galon, Jérôme; Khleif, Samir N; Mellman, Ira; Ohashi, Pamela S; Overwijk, Willem W; Topalian, Suzanne L; Marincola, Francesco M

    2016-01-01

    The Common Rule is a set of ethical principles that provide guidance on the management of human subjects taking part in biomedical and behavioral research in the United States. The elements of the Common Rule were initially developed in 1981 following a revision of the Declaration of Helsinki in 1975. Most academic facilities follow the Common Rule in the regulation of clinical trials research. Recently, the government has suggested a revision of the Common Rule to include more contemporary and streamlined oversight of clinical research. In this commentary, the leadership of the Society for Immunotherapy of Cancer (SITC) provides their opinion on this plan. While the Society recognizes the considerable contribution of clinical research in supporting progress in tumor immunotherapy and supports the need for revisions to the Common Rule, there is also some concern over certain elements which may restrict access to biospecimens and clinical data at a time when high throughput technologies, computational biology and assay standardization is allowing major advances in understanding cancer biology and providing potential predictive biomarkers of immunotherapy response. The Society values its professional commitment to patients for improving clinical outcomes with tumor immunotherapy and supports continued discussion with all stakeholders before implementing changes to the Common Rule in order to ensure maximal patient protections while promoting continued clinical research at this historic time in cancer research.

  14. Data, Model, Conclusions, Doing It Again.

    Science.gov (United States)

    Molenaar, Ivo W.

    1998-01-01

    Explores the robustness of conclusions from a statistical model against variations in model choice with an illustration from G. Box and G. Tiao (1973). Suggests that simultaneous consideration of a class of models for the same data is sometimes superior to analyzing the data under one model and demonstrates advantages to Adaptive Bayesian…

  15. Premature conclusions about psychotherapy for dysthymia

    NARCIS (Netherlands)

    Cuijpers, P.

    2009-01-01

    Dr Cuijpers and Colleagues Reply To the Editor: We thank Dr Gaudiano and colleagues for their contribution to the discussion about psychotherapy for dysthymia. We agree very much with Gaudiano et al that we should be careful about drawing definite conclusions about the comparative efficacy of

  16. Data, model, conclusion, doing it again

    NARCIS (Netherlands)

    Molenaar, W.

    1998-01-01

    This paper explores the robustness of conclusions from a statistical model against variations in model choice (rather than variations in random sampling and random assignment to treatments, which are the usual variations covered by inferential statistics). After the problem formulation in section 1,

  17. Results and conclusion; Resultados e conclusoes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter shows the results and conclusions of the ordered studies by the Science and Technology Ministry from Brazil to the Center of Management and Strategic Studies (CGEE), executed by a multidisciplinary team, most of UNICAMP - State University of Campinas, SP - for evaluation of Brazilian capacity and potential in the production of fuel bioethanol.

  18. 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....

  19. 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.

  20. 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...

  1. Power and Democracy in Denmark. Conclusions

    DEFF Research Database (Denmark)

    Andersen, Jørgen Goul; Christiansen, Peter Munk; Beck Jørgensen, Torben

    In 1997, the Danish Parliament decided to launch a power study, officially An Analysis of Democracy and Power in Denmark. A steering committee consisting of five independent researchers was assigned responsibility for the project. The Steering Committee has gathered the overall conclusions from...... the numerous projects under the Power Study, and this book is a short presentation of these conclusions.The main focus of the book is the state of democracy in Denmark at the dawn of the 21st century. How has democracy fared, has the development made things better or worse, and to which extent does......, and the political institutions show considerable democratic robustness. However, not everything has gone or is going well. There are still pronounced social divisions in Danish society, although their nature has changed somewhat. The ideal of an informed public debate does not always enjoy the best conditions...

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. Natural Killer cell recognition of melanoma: new clues for a more effective immunotherapy

    Directory of Open Access Journals (Sweden)

    Raquel eTarazona

    2016-01-01

    Full Text Available Natural killer cells participate in the early immune response against melanoma and also contribute to the development of an adequate adaptive immune response by their crosstalk with dendritic cells and cytokine secretion. Melanoma resistance to conventional therapies together with its high immunogenicity justifies the development of novel therapies aimed to stimulate effective immune responses against melanoma. However, melanoma cells frequently escape to CD8 T cell recognition by the down-regulation of major histocompatibility complex class I molecules. In this scenario, Natural killer cells emerge as potential candidates for melanoma immunotherapy due to their capacity to recognize and destroy melanoma cells expressing low levels of major histocompatibility complex class I molecules. In addition, the possibility to combine immune checkpoint blockade with other NK cell potentiating strategies (e.g. cytokine induction of activating receptors has opened new perspectives in the potential use of adoptive NK cell-based immunotherapy in melanoma.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Changes of plasma ET and serum IgE levels in children with asthma before and after allergen immunotherapy (AIT)

    International Nuclear Information System (INIS)

    Dai Yunhai; Cheng Guanghua; Xie Jiazhen

    2007-01-01

    Objective: To investigate the relationship between the changes of plasma ET-1, serum IgE levels and allergen immunotherapy(AIT) in children with asthma. Methods: Plasma levels of ET-1 and serum levels of IgE were measured with radioimmunoassay in 46 children with asthma before and after allergen immunotherapy. Results: In 35 patients benefited from allergen immunotherapy, the plasma levels of ET-1 (59.1 ± 11.7pg/ml) and serum levels of IgE (11.1 ± 3.2IU/ml) were higher significantly than those in controls (P 0.05, respectively). Conclusion: These data suggested that the changes of ET-1 and IgE levels after AIT may play an important role in the effective treatment of asthma with AIT. (authors)

  20. Immune Checkpoint Inhibitors: An Innovation in Immunotherapy for the Treatment and Management of Patients with Cancer

    OpenAIRE

    Dine, Jennifer; Gordon, RuthAnn; Shames, Yelena; Kasler, Mary Kate; Barton-Burke, Margaret

    2017-01-01

    Cancer survival rates are generally increasing in the United States. These trends have been partially attributed to improvement in therapeutic strategies. Cancer immunotherapy is an example of one of the newer strategies used to fight cancer, which primes or activates the immune system to produce antitumor effects. The first half of this review paper concisely describes the cell mechanisms that control antitumor immunity and the major immunotherapeutic strategies developed to target these mec...

  1. Superiority in value and the repugnant conclusion

    DEFF Research Database (Denmark)

    Jensen, Karsten Klint

    2007-01-01

    superiority does not amount to a radical value difference at all. I then spell out the consequences of these results for different interpretations of Griffin's suggestion regarding population ethics. None of them comes out very successful, but perhaps they nevertheless retain some interest.......James Griffin has considered a weak form of superiority in value a possible remedy to the Repugnant Conclusion. In this paper, I demonstrate that, in a context where value is additive, this weaker form collapses into a stronger form of superiority. And in a context where value is non-additive, weak...

  2. Two is better than one: advances in pathogen-boosted immunotherapy and adoptive T-cell therapy.

    Science.gov (United States)

    Xin, Gang; Schauder, David M; Zander, Ryan; Cui, Weiguo

    2017-09-01

    The recent tremendous successes in clinical trials take cancer immunotherapy into a new era and have attracted major attention from both academia and industry. Among the variety of immunotherapy strategies developed to boost patients' own immune systems to fight against malignant cells, the pathogen-based and adoptive cell transfer therapies have shown the most promise for treating multiple types of cancer. Pathogen-based therapies could either break the immune tolerance to enhance the effectiveness of cancer vaccines or directly infect and kill cancer cells. Adoptive cell transfer can induce a strong durable antitumor response, with recent advances including engineering dual specificity into T cells to recognize multiple antigens and improving the metabolic fitness of transferred cells. In this review, we focus on the recent prospects in these two areas and summarize some ongoing studies that represent potential advancements for anticancer immunotherapy, including testing combinations of these two strategies.

  3. MHC-I Ligand Discovery Using Targeted Database Searches of Mass Spectrometry Data: Implications for T-Cell Immunotherapies

    DEFF Research Database (Denmark)

    Murphy, J. Patrick; Konda, Prathyusha; Kowalewski, Daniel J.

    2017-01-01

    Class I major histocompatibility complex (MHC-I)-bound peptide ligands dictate the activation and specificity of CD8+ T cells and thus are important for devising T-cell immunotherapies. In recent times, advances in mass spectrometry (MS) have enabled the precise identification of these MHC-I pept...

  4. Surficial uranium deposits: summary and conclusions

    International Nuclear Information System (INIS)

    Otton, J.K.

    1984-01-01

    Uranium occurs in a variety of surficial environments in calcretes, gypcretes, silcretes, dolocretes and in organic sediments. Groundwater moving on low gradients generates these formations and, under favourable circumstances, uranium deposits. A variety of geomorphic settings can be involved. Most surficial deposits are formed in desert, temperate wetland, tropical, or transitional environments. The largest deposits known are in sedimentary environments in arid lands. The deposits form largely by the interaction of ground or surface waters on the geomorphic surface in favourable geologic terrains and climates. The deposits are commonly in the condition of being formed or reconstituted, or being destroyed. Carnotite is common in desert deposits while in wetland deposits no uranium minerals may be seen. Radioactive disequilibrium is common, particularly in wetland deposits. Granites and related rocks are major source rocks and most large deposits are in regions with enriched uranium contents, i.e. significantly greater than 5 ppm uranium. Uranium dissolution and transport is usually under oxidizing conditions. Transport in desert conditions is usually as a bicarbonate. A variety of fixation mechanisms operate to extract the uranium and form the deposits. Physical barriers to groundwater flow may initiate ore deposition. Mining costs are likely to be low because of the near surface occurrence, but there may be processing difficulties as clay may be present and the saline or carbonate content may be high. (author)

  5. CHANGES OF IMMUNE INDEXES DURING SUBLINGUAL ALLERGEN-SPECIFIC IMMUNOTHERAPY IN CHILDREN WITH HAY FEVER

    Directory of Open Access Journals (Sweden)

    I. M. Gaiduk

    2013-01-01

    Full Text Available Aims of study: evaluation of immunological parameters in course of sublingual allergen-specific immunotherapy with tree pollen mixture in children with hay fever.Materials and methods: the study included one-hundred patients 5 to 18 years of age with hay fever (pollen rhinitis, rhinoconjunctivitis and/or asthma. Allergen-specific immunotherapy was administered pre-seasonally for three consecutive years. Cytokinechanges were studied in blood serum and in lavages from nasal cavity. Samples assessed before treatment and after 2nd and 3rd courses SLIT completion.Results: increased serum concentrations of IL-10, IFNγ, and decreased IL-4 contents were revealed in the course of treatment. No significant changes in cytokineconcentrations were detectable in nasal lavages.Conclusions: the changes revealed correspond to a shift of T cell response profile towards Th1 pathway, thus confirming pathogenetic effects of sublingual allergen-specific

  6. 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.

  7. Only one simple conclusion about the climate

    Energy Technology Data Exchange (ETDEWEB)

    Jaremko, G.

    2000-07-24

    Findings concerning climate change, by a three-man team of scientists from the North Dakota Geological Survey, which were presented in a paper read at the Eight International Williston Basin Horizontal Well Workshop, are discussed. The survey by the three scientists covered more than 6,000 scholarly publications. It reported that while the rise in the Earth's temperature is beyond argument, there is anything but agreement as to the causes, or whether the trend is unusual enough to justify concerted and costly actions to change lifestyles. It is shown by direct instrumental measurements that the average temperature at the Earth's surface increased about 0.8 degree Celsius between 1866 and 1998. During that time the concentration of carbon dioxide in the atmosphere increased from 280 to 353 parts per million. While it is generally assumed that the global warming was caused by human activities, new techniques of measurement such as glacier ice coring, dendrochronology (tree-growth rings), lichenometry (measuring the diameter of lichens) and counting concentrations of oxygen 18 and 16 (isotopes whose presence in marine fossils varies depending on temperature) suggest that most of the global warming took place before the increase in carbon dioxide concentration occurred, raising the possibility that the increase in average temperature had causes other than the increase in greenhouse gases. Some of the studies reviewed by the group show that in Europe between ice ages during the Eemian period, some 135,000 to 110,000 years ago, temperature variations of seven degrees Celsius took place; they dropped from two degree Celsius warmer than today to five degree Celsius colder than today. Based on these findings the group's only firm conclusion was that climate is in a continual flux.

  8. 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

  9. 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.

  10. 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.>

  11. 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

  12. Immune Checkpoint Inhibitors: An Innovation in Immunotherapy for the Treatment and Management of Patients with Cancer.

    Science.gov (United States)

    Dine, Jennifer; Gordon, RuthAnn; Shames, Yelena; Kasler, Mary Kate; Barton-Burke, Margaret

    2017-01-01

    Cancer survival rates are generally increasing in the United States. These trends have been partially attributed to improvement in therapeutic strategies. Cancer immunotherapy is an example of one of the newer strategies used to fight cancer, which primes or activates the immune system to produce antitumor effects. The first half of this review paper concisely describes the cell mechanisms that control antitumor immunity and the major immunotherapeutic strategies developed to target these mechanisms. The second half of the review discusses in greater depth immune checkpoint inhibitors that have recently demonstrated tremendous promise for the treatment of diverse solid tumor types, including melanoma, non-small cell lung cancer, and others. More specifically, the mechanisms of action, side effects, and patient and family management and education concerns are discussed to provide oncology nurses up-to-date information relevant to caring for cancer-affected patients treated with immune checkpoint inhibitors. Future directions for cancer immunotherapy are considered.

  13. 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.

  14. Immunotherapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Susan F Slovin

    2016-01-01

    Full Text Available Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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...

  2. 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....

  3. Biogeochemistry of uranium mill wastes program overview and conclusions

    International Nuclear Information System (INIS)

    Dreesen, D.R.

    1981-05-01

    The major findings and conclusions are summarized for research on uranium mill tailings for the US Department of Energy and the US Nuclear Regulatory Commission. An overview of results and interpretations is presented for investigations of 222 Rn emissions, revegetation of tailings and mine spoils, and trace element enrichment, mobility, and bioavailability. A brief discussion addresses the implications of these findings in relation to tailings disposal technology and proposed uranium recovery processes

  4. Summary and Conclusions. Final chapter of Scholarly Communication for Librarians.

    OpenAIRE

    Morrison, Heather

    2008-01-01

    Summary and Conclusions of Scholarly Communication for Librarians, a book designed to provide librarians at all levels with the basics of how scholarly communication works, an understanding of the academic library as an essential support for scholarly communication, the impact of the decisions librarians make, and emerging roles for libraries and librarians in scholarly communication. Includes major points from all chapters, on: scholarship, scholarly journals, the scholarly publishing indus...

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. [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.

  11. Tools for assessing European streams with macroinvertebrates: major results and conclusions from the STAR project

    NARCIS (Netherlands)

    Verdonschot, P.F.M.; Moog, O.

    2006-01-01

    This short paper summarises the information developed in the EU funded research project STAR on autecology databases, metrics, multimetrics and community approaches. For Europe the WFD implementation gave an important stimulus for the development of ecology based assessment techniques. Along with

  12. Targeting NK cells for anti-cancer immunotherapy: clinical and pre-clinical approaches

    Directory of Open Access Journals (Sweden)

    Sebastian eCarotta

    2016-04-01

    Full Text Available The recent success of checkpoint blockade has highlighted the potential of immunotherapy approaches for cancer treatment. While the majority of approved immunotherapy drugs target T cell subsets, it is appreciated that other components of the immune system have important roles in tumor immune-surveillance as well and thus represent promising additional targets for immunotherapy. Natural killer cells are the body’s first line of defense against infected or transformed cells as they kill target cells in an antigen-independent manner. Although several studies have clearly demonstrated the active role of NK cells in cancer-immune surveillance, only few clinically approved therapies currently exist that harness their potential. Our increased understanding of NK cell biology over the past few years has renewed the interest in NK cell based anti-cancer therapies, which has lead to a steady increase of NK cell based clinical and pre-clinical trials. Here, the role of NK cells in cancer immunesurveillance is summarized and several novel approaches to enhance NK cell cytotoxicity against cancer are discussed.

  13. 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...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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...

  19. 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...

  20. Toward Maximizing Immunotherapy in Metastatic Castration-Resistant Prostate Cancer – Rationale for Combinatorial Approaches Using Chemotherapy

    International Nuclear Information System (INIS)

    Slovin, Susan R.

    2012-01-01

    Prostate cancer is particularly suited for active immunotherapy because of the expression of a distinctive number of antigens which are overexpressed on prostate cancer cells and cell lines. There is evidence in this disease that tumors promote immune tolerance starting early in the disease course. As such, chemotherapy, by suppressing tumors and activating immune system homeostatic mechanisms, may help overcome this tumor-induced immune tolerance. Sipuleucel-T which has recently been approved in the US, is an autologous cellular product immunotherapy that induces immune activity likely through activation of dendritic cells. This was associated with a survival benefit in the absence of significant toxicity. However, a post hoc analysis of phase III trial participants found a substantial survival benefit to receiving docetaxel some months after sipuleucel-T. However, another phase III immunotherapy trial combining a prostate cancer therapeutic vaccine GVAX plus docetaxel versus standard docetaxel therapy in advanced prostate cancer, observed a lower overall survival with the vaccine regimen. These trials highlight major unresolved questions concerning the optimum choice, dosing, and timing of chemotherapy relative to active immunotherapy and the overall merits of considering this approach. The ideal treatment approach remains unclear; advances in biomarker validation and trial design may likely improve our ability to assess biologic benefit irrespective of the development of true antitumor immunity.

  1. Toward Maximizing Immunotherapy in Metastatic Castration-Resistant Prostate Cancer – Rationale for Combinatorial Approaches Using Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Slovin, Susan R., E-mail: slovins@mskcc.org [Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan–Kettering Cancer Center, New York, NY (United States)

    2012-05-30

    Prostate cancer is particularly suited for active immunotherapy because of the expression of a distinctive number of antigens which are overexpressed on prostate cancer cells and cell lines. There is evidence in this disease that tumors promote immune tolerance starting early in the disease course. As such, chemotherapy, by suppressing tumors and activating immune system homeostatic mechanisms, may help overcome this tumor-induced immune tolerance. Sipuleucel-T which has recently been approved in the US, is an autologous cellular product immunotherapy that induces immune activity likely through activation of dendritic cells. This was associated with a survival benefit in the absence of significant toxicity. However, a post hoc analysis of phase III trial participants found a substantial survival benefit to receiving docetaxel some months after sipuleucel-T. However, another phase III immunotherapy trial combining a prostate cancer therapeutic vaccine GVAX plus docetaxel versus standard docetaxel therapy in advanced prostate cancer, observed a lower overall survival with the vaccine regimen. These trials highlight major unresolved questions concerning the optimum choice, dosing, and timing of chemotherapy relative to active immunotherapy and the overall merits of considering this approach. The ideal treatment approach remains unclear; advances in biomarker validation and trial design may likely improve our ability to assess biologic benefit irrespective of the development of true antitumor immunity.

  2. 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)

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  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. 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.

  12. The immunotherapy of canine osteosarcoma: a historical and systematic review.

    Science.gov (United States)

    Wycislo, K L; Fan, T M

    2015-01-01

    Osteosarcoma is a malignant mesenchymal neoplasm that accounts for the majority of primary bone tumors in dogs and shares biological and clinical similarities with osteosarcoma in humans. Despite dose intensification with conventional cytotoxic therapies, survival times for dogs and humans diagnosed with high-grade osteosarcoma have not changed in the past 20 years, with the principal cause of mortality being the development of pulmonary metastases. Given the therapeutic plateau reached for delaying metastatic progression with cytotoxic agents, exploration of alterative adjuvant therapies for improving management of osteosarcoma micrometastases is clinically justified. Evidence suggests that osteosarcoma is an immunogenic tumor, and development of immunotherapies for the treatment of microscopic lung metastases might improve long-term outcomes. In this review, the history and foundational knowledge of immune interactions to canine osteosarcoma are highlighted. In parallel, immunotherapeutic strategies that have been explored for the treatment of canine osteosarcoma are summarized. With a greater understanding and awareness for how the immune system might be redirected toward combating osteosarcoma metastases, the rational development of diverse immune strategies for managing osteosarcoma holds substantial promise for transforming the therapeutic landscape and improving disease management in both dogs and human beings. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  13. 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

  14. 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.

  15. [Allergen immunotherapy: Mechanisms of action, and therapeutic and socioeconomic impact Consensus of the Asociación Colombiana de Alergia, Asma e Imunología].

    Science.gov (United States)

    Sánchez, Jorge; Cardona, Ricardo; Caraballo, Luis; Serrano, Carlos; Ramírez, Ruth; Díez, Susana; García, Elizabeth; Segura, Ana María; Cepeda, Alfonso; Minotas, María

    2016-09-01

    Allergies comprise a set of highly prevalent diseases. When allergic processes are not controlled, they can endanger patients' health and lives, and have an important economic and social impact. The aim of this paper is to present a practical consensus of the scientific evidence on the use of immunotherapy in allergic diseases. A collaborative review made by various institutes and universities in Colombia was carried out upon request of the Asociación Colombiana de Alergia, Asma e Imunología, led by general practitioners, allergists, immunologists, internists and paediatricians with experience in the field of allergies. As a result, based on current national and international scientific evidence, we describe in detail what immunotherapy is about, its indications, contraindications and its economic and health benefits. Conclusions show immunotherapy as a clinically effective and safe treatment, which can substantially reduce the cost of the overall treatment of allergic patients.

  16. Evaluation of two grass pollen extracts for immunotherapy by serum determinations of specific IgE and IgG4 antibodies towards purified Timothy grass pollen allergens (Phl p 1, 2, 4, 5, 6, 7, 11, 12 in patients undergoing hyposensitization treatment

    Directory of Open Access Journals (Sweden)

    Renato Enzo Rossi

    2002-01-01

    Conclusions: These results indicate that grass pollen immunotherapy elicits an array of antibody specificities that reflect the allergen content and the potency of allergen extracts; this could be of pivotal importance to define optimal allergen extract doses.

  17. The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Bødtger, Uffe; Poulsen, L K; Jacobi, H H

    2002-01-01

    BACKGROUND: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North Americ...

  18. 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

  19. An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis.

    Science.gov (United States)

    Wong, S H; Saunders, M D; Larner, A J; Das, K; Hart, I K

    2010-10-01

    Voltage-gated potassium channel antibody-positive limbic encephalitis (VGKC+LE) frequently improves with immunotherapy, although the optimum regimen is unknown. The effectiveness of a combination immunomodulatory regimen was tested in consecutive VGKC+LE patients. This was an open-label prospective study of nine VGKC+LE patients. All patients had plasma exchange (50 ml/kg), intravenous immunoglobulin (2 g/kg) and intravenous methylprednisolone (1 g×3), followed by maintenance oral prednisolone (1 mg/kg/day). Mycophenolate (2 g/day) was used in the first three patients. Assessments included serial clinical, cognitive, brain MRI and VGKC antibody testing. Within 1 week, seizures and hyponatraemia remitted in all affected patients. Cognitive function improved in all patients within 3 months. MRI appearances improved substantially within 9 months, with remission of inflammation in the majority of patients. All achieved immunological remission with normal VGKC antibody titres within 1-4 months. Major adverse events of therapy included one septicaemia and one thrombosis on plasma exchange and one death from sepsis after incidental bowel surgery. One patient remains in remission after 40 months of follow up, 26 months after being off all treatment. Our immunotherapy regimen was effective for the treatment of the clinical, cognitive and immunological features of VGKC+LE. Radiological improvement was seen in the majority. Pending randomised controlled trials, this regimen is proposed for the treatment of VGKC+LE.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. The no conclusion intervention for couples in conflict.

    Science.gov (United States)

    Migerode, Lieven

    2014-07-01

    Dealing with difference is central to all couple therapy. This article presents an intervention designed to assist couples in handling conflict. Central to this approach is the acceptance that most conflicts cannot be solved. Couples are in need of a different understanding of couples conflict. This understanding is found in the analysis of love in context and in relational dialectics. Couples are guided through different steps: deciding on the valence of the issue as individuals, helping them decide which differences can be resolved and which issues demand new ways of living with the inevitable, and the introduction in the suggested no conclusion dialogue. This article briefly describes the five day intensive couple therapy program, in which the no intervention is embedded. The theoretical foundation of the intervention, followed by the step by step description of the intervention forms the major part of the article. A case vignette illustrates this approach. © 2012 American Association for Marriage and Family Therapy.

  9. Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy.

    Science.gov (United States)

    Van Ree, R; Van Leeuwen, W A; Dieges, P H; Van Wijk, R G; De Jong, N; Brewczyski, P Z; Kroon, A M; Schilte, P P; Tan, K Y; Simon-Licht, I F; Roberts, A M; Stapel, S O; Aalberse, R C

    1997-01-01

    IgE titres tend to rise early after the start of immunotherapy, followed by a decline to pre-immunotherapy levels or lower. We were interested to know whether the early increase in IgE antibodies includes new specificities of IgE, and whether these responses persist. Sera of 64 patients undergoing grass pollen immunotherapy were tested for IgE against four purified grass pollen allergens: Lol p 1, 2, 3, and 5. At least two serum samples were taken, one before the start of therapy and one between 5 and 18 months after the first immunization (mean: 10 months). The mean IgE responses to Lol p 1, 2 and 3 showed a moderate but not significant increase. In contrast, the mean IgE response to Lol p 5 showed a significant decrease of > 30%. IgE against total Lohum perenne pollen extract moderately increased (> 20%), showing that a RAST for total pollen is not always indicative for the development of IgE against its major allergens. For > 40% of the patients it was found that IgE against one or more of the four allergens increased, while IgE against the remaining allergen(s) decreased. For 10 sera the ratio of IgE titres against at least two allergens changed by at least a factor of 5. The changes in specific IgE also included conversions from negative (< 0.1 RU) to positive (0.6 to 5.0 RU) for five patients. For two patients, the induction of these 'new' IgE antibodies against major allergens was shown to result in a response that was persistent over several years. Although active induction of new IgE specificities by immunotherapy was not really proven, the observations in this study indicate that monitoring of IgE against purified (major) allergens is necessary to evaluate changes in specific IgE in a reliable way.

  10. 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

  11. 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.

  12. 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.

  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. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Immuno-pharmacodynamics for evaluating mechanism of action and developing immunotherapy combinations.

    Science.gov (United States)

    Parchment, Ralph E; Voth, Andrea Regier; Doroshow, James H; Berzofsky, Jay A

    2016-08-01

    Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule). Clinical pharmacodynamic (PD) biomarkers will be useful endpoints for confirming drug mechanism of action, evaluating combination therapies for synergy or antagonism, and identifying optimal dosage regimens. In contrast to conventional PD in which drug action occurs entirely within a single target cell (ie, is self-contained within the malignant cell), immunotherapy involves a complex mechanism of action with sequential steps that propagate through multiple cell types, both normal and malignant. Its intercellular pharmacology begins with molecular target engagement either on an immune effector cell or a malignant cell, followed by stimulatory biochemical and biological signals in immune effector cells, and then finally ends with activation of cell death mechanisms in malignant cells lying within a certain distance from the activated effector cells (immune cell-tumor cell proximity). Evaluating such "trans-cellular pharmacology," in which different steps of drug action are distributed across multiple cell types, requires novel microscopy and image analysis tools capable of quantifying PD-biomarker responses, mapping the responses onto the cellular geography of the tumor using phenotypic biomarkers to identify specific cell types, and finally analyzing the spatial relationships between biomarkers in the context of each cell's biological role. We have termed this form of nearest neighbor image analysis of drug action "proximity PD microscopy," to indicate the

  1. FAST: towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies

    Directory of Open Access Journals (Sweden)

    Zuidmeer-Jongejan Laurian

    2012-03-01

    Full Text Available 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 aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1 and lipid transfer protein (Pru p 3, respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models, SCIT with alum-absorbed hypoallergens will be evaluated in phase I/IIa and IIb randomized double-blind placebo-controlled (DBPC clinical trials, with the DBPC food challenge as primary read-out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication.

  2. FAST: towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies

    Science.gov (United States)

    2012-01-01

    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 aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1) and lipid transfer protein (Pru p 3), respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models), SCIT with alum-absorbed hypoallergens will be evaluated in phase I/IIa and IIb randomized double-blind placebo-controlled (DBPC) clinical trials, with the DBPC food challenge as primary read-out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication. PMID:22409908

  3. Immuno-therapy of Acute Radiation Syndromes : Extracorporeal Immuno-Lympho-Plasmo-Sorption.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Methods Results Summary and conclusions Introduction: Existing Medical Management of the Acute Radiation Syndromes (ARS) does not include methods of specific immunotherapy and active detoxication. Though the Acute Radiation Syndromes were defined as an acute toxic poisonous with development of pathological processes: Systemic Inflammatory Response Syndrome (SIRS), Toxic Multiple Organ Injury (TMOI), Toxic Multiple Organ Dysfunction Syndrome(TMODS), Toxic Multiple Organ Failure (TMOF). Radiation Toxins of SRD Group play an important role as the trigger mechanisms in development of the ARS clinical symptoms. Methods: Immuno-Lympho-Plasmo-Sorption is a type of Immuno-therapy which includes prin-ciples of immunochromato-graphy, plasmopheresis, and hemodialysis. Specific Antiradiation Antitoxic Antibodies are the active pharmacological agents of immunotherapy . Antiradia-tion Antitoxic Antibodies bind selectively to Radiation Neurotoxins, Cytotoxins, Hematotox-ins and neutralize their toxic activity. We have developed the highly sensitive method and system for extracorporeal-immune-lypmh-plasmo-sorption with antigen-specific IgG which is clinically important for treatment of the toxic and immunologic phases of the ARS. The method of extracorporeal-immune-lypmh-plasmo-sorption includes Antiradiation Antitoxic Antibodies (AAA) immobilized on microporous polymeric membranes with a pore size that is capable to provide diffusion of blood-lymph plasma. Plasma of blood or lymph of irradiated mammals contains Radiation Toxins (RT) that have toxic and antigenic properties. Radiation Toxins are Antigen-specific to Antitoxic blocking antibodies (Immunoglobulin G). Plasma diffuses through membranes with immobilized AAA and AA-antibodies bind to the polysaccharide chain of tox-ins molecules and complexes of AAA-RT that are captured on membrane surfaces. RT were removed from plasma. Re-transfusion of plasma of blood and lymph had been provided. We show a statistical significant

  4. TH-C-17A-11: Hyperthermia-Driven Immunotherapy Using Non-Invasive Radiowaves

    Energy Technology Data Exchange (ETDEWEB)

    Serda, R; Savage, D; Corr, S; Curley, S [Baylor College of Medicine, Houston, TX (United States)

    2014-06-15

    Purpose: The sad truth is that cancer is blamed for the death of nearly one in four people in the US. Immunotherapy offers hope for stimulating cancer immunity leading to targeted killing of cancer cells and a preventative measure for cancer recurrence. Unfortunately, the clinical efficacy of immunotherapy has not yet been established, however novel approaches are being developed, including combining immunotherapy with traditional chemotherapy, radiotherapy or thermal therapy. Therapeutics such as radiofrequency (RF) ablation and select chemotherapeutics induce mild anticancer immune responses. This project seeks to enhance the immune responses stimulated by these agents by co-delivery of nanoparticle-based chemotherapeutics and immune modulators in the presence of RF induced hyperthermia. Methods: A 4T1 mouse model of breast cancer is used to test the ability of RF waves to enhance accumulation of nanoparticles in tumor tissue by increasing blood flow and extravation of nanoparticles from hyperpermeable vessels. Images of particle and cell trafficking in the tumor are captured using an integrated RF and confocal imaging system, and tumor growth is monitored by tumor bioluminescence and caliper measurements. Results: Here we demonstrate enhanced intratumoral blood flow induced by non-invasive RF waves and an increase in nanoparticle accumulation in the tumor. IL-12 is shown to have powerful anti-tumor effects leading to tumor regression and the release of Th1-biased cytokines. Doxorubicin nanoparticles combined with adjuvant nanoparticles exhibited superior antitumor effects to single agent therapy. Conclusion: RF therapy combined with nanotherapeutics is a promising approach to enhance the delivery of therapeutics to the tumor and to stimulate a tumor microenvironment that supports the development of cancer-specific immune responses. This research was supported by the National Institute of Health grant numbers U54 CA143837 and U54 CA151668, and the Kanzius

  5. TH-C-17A-11: Hyperthermia-Driven Immunotherapy Using Non-Invasive Radiowaves

    International Nuclear Information System (INIS)

    Serda, R; Savage, D; Corr, S; Curley, S

    2014-01-01

    Purpose: The sad truth is that cancer is blamed for the death of nearly one in four people in the US. Immunotherapy offers hope for stimulating cancer immunity leading to targeted killing of cancer cells and a preventative measure for cancer recurrence. Unfortunately, the clinical efficacy of immunotherapy has not yet been established, however novel approaches are being developed, including combining immunotherapy with traditional chemotherapy, radiotherapy or thermal therapy. Therapeutics such as radiofrequency (RF) ablation and select chemotherapeutics induce mild anticancer immune responses. This project seeks to enhance the immune responses stimulated by these agents by co-delivery of nanoparticle-based chemotherapeutics and immune modulators in the presence of RF induced hyperthermia. Methods: A 4T1 mouse model of breast cancer is used to test the ability of RF waves to enhance accumulation of nanoparticles in tumor tissue by increasing blood flow and extravation of nanoparticles from hyperpermeable vessels. Images of particle and cell trafficking in the tumor are captured using an integrated RF and confocal imaging system, and tumor growth is monitored by tumor bioluminescence and caliper measurements. Results: Here we demonstrate enhanced intratumoral blood flow induced by non-invasive RF waves and an increase in nanoparticle accumulation in the tumor. IL-12 is shown to have powerful anti-tumor effects leading to tumor regression and the release of Th1-biased cytokines. Doxorubicin nanoparticles combined with adjuvant nanoparticles exhibited superior antitumor effects to single agent therapy. Conclusion: RF therapy combined with nanotherapeutics is a promising approach to enhance the delivery of therapeutics to the tumor and to stimulate a tumor microenvironment that supports the development of cancer-specific immune responses. This research was supported by the National Institute of Health grant numbers U54 CA143837 and U54 CA151668, and the Kanzius

  6. Airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    Hua Xiang

    2016-07-01

    Full Text Available Objective: To evaluate the airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy. Methods: A total of 68 children with dust mite allergic rhinitis treated in our hospital from November, 2012 to October, 2015 were selected as the research subjects and randomly divided into observation group 34 cases and control group 34 cases. The control group received clinical routine therapy for allergic rhinitis, the observation group received sublingual immunotherapy, and then differences in basic lung function indicator values, small airway function indicator values and levels of serum inflammatory factors as well as serum ECP, TARC, Eotaxin-2 and VCAM were compared between two groups after treatment. Results: The FVC, FEV1, PEF and FEV1/FVC values of the observation group after treatment were higher than those of the control group (P<0.05; the MMEF, MEF50% and MEF25% values of the observation group were higher than those of the control group, and the proportion of AHR was lower than that of the control group (P<0.05; the serum IL-4, IL-9, IL-12, IL-13 and IL-16 levels of the observation group after treatment were lower than those of the control group, and the IL-10 and IL-12 levels are higher than those of the control group (P<0.05; the serum ECP, TARC, Eotaxin-2 and VCAM levels of the observation group children after treatment were lower than those of the control group (P<0.05. Conclusions: Sublingual immunotherapy for children with dust mite allergic rhinitis can optimize the airway function, reduce the systemic inflammatory response and eventually improve the children’s overall state, and it’s has positive clinical significance.

  7. Immunotherapy with intralesional Candida albicans antigen in resistant or recurrent warts: A study

    Directory of Open Access Journals (Sweden)

    Imran Majid

    2013-01-01

    Full Text Available Background: Warts are sometimes resistant or they tend to recur after every possible destructive therapy. Immunotherapy with skin-test antigens has been used as a viable therapeutic option in such recalcitrant cases. Aim: The aim of the study was to evaluate the response of resistant or recurrent warts to intralesional Candida albicans antigen immunotherapy. Materials and Methods: A total of 40 patients with resistant or recurrent warts who showed a positive test reaction to C. albicans antigen were given intralesional injections of purified C. albicans antigen solution in a single wart at 3-weekly intervals for a total of three doses. The patients were monitored for resolution of the injected wart as well as other untreated warts. The patients who responded positively were then followed up for any relapses over the next 6 months. Adverse events, if any, were also documented. Results: Of the 40 patients enrolled in the study, 34 completed the total treatment protocol of three injections and 6 months of follow-up. In these 34 patients, 19 (56% showed a complete resolution of warts at all places on the body. In addition, two patients (6% showed a partial or complete resolution of the treated wart, but there was no effect on the untreated warts. Thirteenpatients (38% failed to show any response to the treatment regimen. In all patients showing resolution of all the warts, there were no relapses at any site over the next 6 months of follow-up. The most common adverse effect seen was pain during the intralesional injection. Conclusions: Intralesional Candida immunotherapy seems to be an effective treatment option in more than half of the patients who fail to show a positive response to destructive modes of treatment or in whom there are multiple recurrences. Limitations: The small sample size and lack of control group are the main limitations of the study.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Carbon anhydrase IX specific immune responses in patients with metastatic renal cell carcinoma potentially cured by interleukin-2 based immunotherapy

    DEFF Research Database (Denmark)

    Rasmussen, Susanne; Donskov, Frede; Pedersen, Johannes W

    2013-01-01

    Abstract The majority of clear-cell renal cell carcinomas (ccRCC) show high and homogeneous expression levels of the tumor associated antigen (TAA) carbonic anhydrase IX (CAIX), and treatment with interleukin-2 (IL-2) based immunotherapy can lead to cure in patients with metastatic renal cell...... of disease (NED) following treatment with IL-2 based immunotherapy, and thus potentially cured. Immune reactivity in these patients was compared with samples from patients with dramatic tumor response obtained immediately at the cessation of therapy, samples from patients that experienced progressive disease...... interest in future cancer vaccines, but more studies are needed to elucidate the immunological mechanisms of action in potentially cured patients treated with an immunotherapeutic agent....

  19. The evidence for biologic immunotherapy in Sarcoidosis: A systematic review

    Directory of Open Access Journals (Sweden)

    Pooja Shah

    2017-09-01

    Full Text Available Background Sarcoidosis is a chronic inflammatory disease with a myriad of clinical manifestations. Treatment involves immunosuppression with corticosteroids or steroid-sparing agents. A proportion of patients does not respond to or are intolerant to therapy. Targeted immunotherapy with biologic agents has emerged as a novel approach with plausible mechanistic reasons to warrant study. Aims The aim of this review was to evaluate the evidence for the efficacy of biological therapy in sarcoidosis. Methods We conducted a systematic literature review and meta-analysis of all published randomised-controlled trials (RCT evaluating biological therapy in sarcoidosis, using MEDLINE and Embase databases, through to September 2017. The search terms included sarcoidosis, infliximab, adalimumab, etanercept, golimumab, certolizumab, rituximab, abatacept, tocilizumab, anakinra, ustekinumab, secukinumab. Only articles reporting RCTs were selected. Improvements in respiratory disease were assessed by changes in forced vital capacity (FVC by weighted mean difference (WMD. There were insufficient data on outcome measures in other organ systems to comparatively assess efficacy. Results The search identified 2,324 studies of which only 5 provided relevant and original data. This comprised a total of 364 patients, evaluating pulmonary, cutaneous and ocular sarcoidosis. One study in pulmonary disease and one study in cutaneous disease demonstrated improvements in the primary outcome. In pulmonary disease, meta-analysis of the treatment effect of anti-TNF therapy versus placebo on FVC revealed a WMD of 1.69 per cent (95 per cent confidence interval, 1.44–1.94. Conclusion There are insufficient data to suggest the long-term efficacy of anti-TNFα inhibitors in the treatment of sarcoidosis. This may be due to heterogeneity, small sample sizes and the lack of consistent reporting of outcome measures.

  20. Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells.

    Science.gov (United States)

    Cirone, Pasquale; Bourgeois, Jacqueline M; Shen, Feng; Chang, Patricia L

    2004-10-01

    An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma-bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated.

  1. ALLERGEN-SPECIFIC IMMUNOTHERAPY: VACCINES FOR ALLERGIC DISEASES

    Directory of Open Access Journals (Sweden)

    A. S. Fedorov

    2015-01-01

    Full Text Available Allergen-specific immunotherapy (ASIT is the most effective method of allergy treatment which consists of exposure to small doses of antigen responsible for development of allergic condition in the particular patient. Therefore, one may achieve desensitization to this antigen. The history of ASIT application lasts for more than 100 years, and, over this time, huge clinical evidence for the usage of the method has been accumulated. Use of ASIT causes reduction of allergy symptoms and treatment needs and, moreover, it has the potential for long-term clinical benefit, by preventing the development of allergy and its symptoms. The treatment affects basic immunological mechanisms responsible for the development of clinical symptoms. ASIT is an antiinflammatory, pathogenetic and prophylactic treatment of allergic airway disease. The review considers the results of major clinical trials of the ASIT applications for treatment of allergic diseases of the respiratory system (allergic rhinitis and bronchial asthma. Various schemes of ASIT are discussed including its different variants (injectable and sublingual ASIT, the issues of preparation choice for ASIT from those currently available on the pharmaceutical market, patient selection criteria, and the issues of modern molecular allergodiagnostic (allergic sensitization mapping of the patient at molecular level, in order to optimize them. Immunological mechanisms of ASIT are also considered, since appropriate views are rather contraversial. The ASIT effect is mediated through the following basic immunological mechanisms: the suppressed increase of the eosinophil concentrations, reduced duration of the delayed hypersensitivity phase, as well as initiation and maintenance of the Th2-to-Th1-like immune response transition. Regulatory T-cells play a major role in implementation of the immunological mechanism in ASIT, they have a significant impact on the Th2 response suppression. Such suppression may proceed

  2. The research status of immune checkpoint blockade by anti-CTLA4 and anti-PD1/PD-l1 antibodies in tumor immunotherapy in China

    Science.gov (United States)

    Zhao, Xiaoqin; He, Liangmei; Mao, Kaiyun; Chen, Daming; Jiang, Hongbo; Liu, Zhiping

    2018-01-01

    Abstract Purpose: Using bibliometrics, we analyzed the research status of immune checkpoint blockade (ICB, a popular tumor immunotherapy method represented by antibodies targeted CTLA-4 and PD-1/PD-L1) in tumor immunotherapy in China during the past 2 decades. Methods: Articles in Science Citation Index Expanded (SCI-EXPANDED), patents in Thomson Innovation, and drugs in Cortellis Competitive Intelligence in the field of ICB for tumor immunotherapy from 1996 to 2015 were the subjects of bibliometric analysis. Using database-attached software and Excel, quantitative analyses were performed including examination of the number of documents, citation frequency, h-index, key projects, quantity of publications, public patents, and status of new drug research. Results: The number of publications from 1996 to 2015 in the field of ICB for tumor immunotherapy that came out of China was 380, which was 14.3% of the total publications worldwide and was second only to that of the USA. In the past decade, China has rapidly increased the number of publications and patents in this field. However, indicators of publication influence, such as citation frequency and h-index, were far behind other advanced countries. In addition, the total number of patents in China was much lower than that of the USA. China has introduced 5 drugs for ICB that are being developed for the healthcare market. Conclusion: Tumor immunotherapy research such as ICB in China has developed rapidly with increasing influence in the last 2 decades. However, there is still a relatively large gap compared with the USA. It is expected that China will have greater influence on tumor immunotherapy research in the near future. PMID:29642147

  3. Allergen immunotherapy: clinical and practical education of Italian trainees in allergy and clinical immunology schools.

    Science.gov (United States)

    Ridolo, E; Incorvaia, C; Senna, G E; Montagni, M; Olivieri, E; Canonica, G W

    2013-10-01

    We performed a survey, based on a questionnaire including 20 items, submitted anonymously to Italian trainees in Allergology and Clinical Immunology, in order to obtain information about their specific allergen immunotherapy (AIT) practices. The questionnaire was sent to 40 trainees, who had attended the last two years of the training course. Thirty-four subjects (mean age: 27 years, 65% females) adequately completed the survey. The answers to the questionnaire showed that only 60% of the training programs included lectures on AIT. Among the trainees using AIT, only 40% declared being able to prescribe it independently, while 60% were guided by a tutor. Of the trainees who were able to prescribe AIT autonomously, 60% were familiar with both routes of administration, i.e. subcutaneous (SCIT) and sublingual immunotherapy (SLIT), while 25% of these used only SLIT. In 80% of the training institutions involved, the trainees could attend a dedicated AIT outpatient ward for SCIT administration; only 40% administered AIT personally, and in half of these cases, they were guided by a tutor. Only 70% of trainees had experience in the follow-up of patients still under treatment and of patients who had completed treatment. Analysis of the answers obtained for questions on venom immunotherapy (VIT) showed that, in 90% of cases, the trainees attended a dedicated outpatients ward where VIT is administered, but with a role limited to observation/cooperation. Only 30% were involved in the follow-up of patients who were under treatment or who had completed VIT. Only 20% of the trainees felt confident enough about VIT to prescribe this treatment independently, 80% knew there were several administration protocols, and the majority prescribed products from three different manufacturers. These findings suggest that there is significant room for improving the instructions provided regarding allergology and clinical immunology to trainees in Italy with respect to AIT.

  4. 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....

  5. 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...

  6. 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

  7. 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...

  8. 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.

  9. Major depression

    Science.gov (United States)

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... providers do not know the exact causes of depression. It is believed that chemical changes in the ...

  10. 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

  11. Summary of the discussion, Conclusion of the meeting

    International Nuclear Information System (INIS)

    Crutzen, S.

    1997-01-01

    The discussion was organised in three major periods corresponding to the main themes developed by the programme of the meeting: the qualification approaches, the qualification experience accumulated so far, one particular frame or motivation of the ISI qualification: the risk based (or informed) ISI. The qualification approaches presented by national representatives raised few questions. More discussion was induced on the qualification concepts, responsibilities, need and writing of the technical justification, motivation for the open trials, similitude between concepts, benefit deriving from the qualification of inspection procedures and further motivation. the conclusion could be as the following: the evolution of qualification applications, even if issued from harmonised concepts, appears to be nationalistically based. It is a thought that emulation and harmonisation could actually produce both savings and improvements in this area. 'The wheel does not have to be re-invented in each country' and it is the declared objective of ENIQ. There seems to be a need for some international agreement in the setting of standards for qualification. One area which seems to continue to be of underlying concern is in the characterisation of defects. There seems to be a need for appropriate 'defected blocks' satisfying the criteria of representativeness, quality, low cost, reproducibility, etc. More specific cases of Technical Justification development are needed to serve as examples and incentive for the case of this element of inspection qualification

  12. 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.

  13. 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.

  14. Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT in mice

    Directory of Open Access Journals (Sweden)

    Mondoulet Lucie

    2012-11-01

    Full Text Available Abstract Background Epicutaneous immunotherapy (EPIT on intact skin with an epicutaneous delivery system has already been used in preclinical and clinical studies. In epicutaneous vaccination and immunotherapy, the stripping of skin before application of the allergen is suggested to facilitate the passage of allergen through immune cells. Objectives The aim of this study was to compare the immunological response induced by EPIT performed on intact and stripped skin in a mouse model of peanut allergy. Methods After oral sensitization with peanut and cholera toxin, BALB/c mice were epicutaneously treated using an epicutaneous delivery system (Viaskin® (DBV Technologies, Paris applied either on intact skin or on stripped skin. Following EPIT, mice received an exclusive oral peanut regimen, aimed at triggering esophageal and jejunal lesions. We assessed eosinophil infiltration by histology, mRNA expression in the esophagus, antibody levels and peripheral T-cell response. Results EPIT on intact skin significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (2.7 ± 0.9, compared to Sham 19.9 ± 1.5, p  Conclusions Epicutaneous allergen-specific immunotherapy needs the integrity of superficial layers of the stratum corneum to warranty safety of treatment and to induce a tolerogenic profile of the immune response.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. 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.

  3. 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...

  4. 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

  5. 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.

  6. 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...

  7. 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...

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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, ...

  15. 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

  16. 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

  17. 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.

  18. [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.

  19. 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...

  20. 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.

  1. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

    Directory of Open Access Journals (Sweden)

    M J Pont

    Full Text Available Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage-restricted expression as potential targets for immunotherapy of hematological cancers.

  2. NK cell-based cancer immunotherapy: from basic biology to clinical application.

    Science.gov (United States)

    Li, Yang; Yin, Jie; Li, Ting; Huang, Shan; Yan, Han; Leavenworth, JianMei; Wang, Xi

    2015-12-01

    Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.

  3. 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

  4. 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.

  5. Ex vivo generation of human alloantigen-specific regulatory T cells from CD4(posCD25(high T cells for immunotherapy.

    Directory of Open Access Journals (Sweden)

    Jorieke H Peters

    Full Text Available BACKGROUND: Regulatory T cell (Treg based immunotherapy is a potential treatment for several immune disorders. By now, this approach proved successful in preclinical animal transplantation and auto-immunity models. In these models the success of Treg based immunotherapy crucially depends on the antigen-specificity of the infused Treg population. For the human setting, information is lacking on how to generate Treg with direct antigen-specificity ex vivo to be used for immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that in as little as two stimulation cycles with HLA mismatched allogeneic stimulator cells and T cell growth factors a very high degree of alloantigen-specificity was reached in magnetic bead isolated human CD4(posCD25(high Treg. Efficient increases in cell numbers were obtained. Primary allogeneic stimulation appeared a prerequisite in the generation of alloantigen-specific Treg, while secondary allogeneic or polyclonal stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies enriched alloantigen-specificity and cell yield to a similar extent. CONCLUSIONS/SIGNIFICANCE: The ex vivo expansion protocol that we describe will very likely increase the success of clinical Treg-based immunotherapy, and will help to induce tolerance to selected antigens, while minimizing general immune suppression. This approach is of particular interest for recipients of HLA mismatched transplants.

  6. Number of objectives and conclusions in dissertations and thesis

    Directory of Open Access Journals (Sweden)

    Liebano Richard Eloin

    2005-01-01

    Full Text Available PURPOSE: To analyze the number of objectives and conclusions presented in dissertations and thesis defended at Federal University of São Paulo - Paulista School of Medicine (UNIFESP - EPM. METHODS: It was realized a search in the master degree dissertations and doctor degree thesis defended at Federal University of São Paulo - Paulista School of Medicine in the years 2002 and 2003 that were found available in the central library of this university. RESULTS: From 723 master dissertations analyzed, 62 (8,57% presented only one objective and one conclusion, 134 (18,53% presented one objective and more than one conclusion and 527 (72,89% had more than one objective and more than one conclusion. From 502 doctor thesis analyzed, 23 (4,58% presented only one objective and one conclusion, 123 (24,50% presented one objective and more than one conclusion and 376 (74,90% had more than one objective and more than one conclusion.. CONCLUSIONS: It wasn't found in researched literature the number of objectives and conclusions a scientific work must have. A highest number of thesis and dissertations presented more than one objective and more than one conclusion.

  7. MRl of prostate cancer antigen expression for diagnosis and immunotherapy.

    Directory of Open Access Journals (Sweden)

    Jing Ren

    Full Text Available BACKGROUND: Tumor antigen (TA-targeted monoclonal antibody (mAb immunotherapy can be effective for the treatment of a broad range of cancer etiologies; however, these approaches have demonstrated variable clinical efficacy for the treatment of patients with prostate cancer (PCa. An obstacle currently impeding translational progress has been the inability to quantify the mAb dose that reaches the tumor site and binds to the targeted TAs. The coupling of mAb to nanoparticle-based magnetic resonance imaging (MRI probes should permit in vivo measurement of patient-specific biodistributions; these measurements could facilitate future development of novel dosimetry paradigms wherein mAb dose is titrated to optimize outcomes for individual patients. METHODS: The prostate stem cell antigen (PSCA is broadly expressed on the surface of prostate cancer (PCa cells. Anti-human PSCA monoclonal antibodies (mAb 7F5 were bound to Au/Fe(3O(4 (GoldMag nanoparticles (mAb 7F5@GoldMag to serve as PSCA-specific theragnostic MRI probe permitting visualization of mAb biodistribution in vivo. First, the antibody immobilization efficiency of the GoldMag particles and the efficacy for PSCA-specific binding was assessed. Next, PC-3 (prostate cancer with PSCA over-expression and SMMC-7721 (hepatoma cells without PSCA expression tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI. MRI probe biodistributions were assessed at increasing time intervals post-infusion; therapy response was evaluated with serial tumor volume measurements. RESULTS: Targeted binding of the mAb 7F5@GoldMag probes to PC-3 cells was verified using optical images and MRI; selective binding was not observed for SMMC-7721 tumors. The immunotherapeutic efficacy of the mAb 7F5@GoldMag in PC-3 tumor-bearing mice was verified with significant inhibition of tumor growth compared to untreated control animals. CONCLUSION: Our promising results suggest the feasibility of using mAb 7F5@GoldMag probes as a

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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)

  18. 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

  19. 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.

  20. hrHPV E5 oncoprotein: immune evasion and related immunotherapies.

    Science.gov (United States)

    de Freitas, Antonio Carlos; de Oliveira, Talita Helena Araújo; Barros, Marconi Rego; Venuti, Aldo

    2017-05-25

    The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions. Thus, insofar as the majority of cervical, oropharyngeal and anal cancers are caused by high-risk HPV (hrHPV), mainly by HPV16, the aim of this review is to discuss the immune pathways interfered by E5 oncoprotein of hrHPV highlighting the various aspects of the potential immunotherapeutic approaches.

  1. [Current Status and Challenges of CAR-T Immunotherapy in Hematologic Malignancies -Review].

    Science.gov (United States)

    Cheng, Xin; Wang, Ya-Jie; Feng, Shuai; Wu, Ya-Yun; Yang, Tong-Hua; Lai, Xun

    2018-04-01

    The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment. In this review, the history, structure and mechanism of action of CAR-T, as well as the current status and challenges of CAR-T immunotherapy in acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma are summarized.

  2. Chimeric Antigen Receptor-Engineered T Cells in Tumor Immunotherapy: From Bench to Beside

    Directory of Open Access Journals (Sweden)

    Peng WANG

    2017-06-01

    Full Text Available Chimeric antigen receptor-engineered T cells (CAR-T cells, a classification of cultured T cells after modification of gene engineering technology, can recognize specific tumor antigens in a major histocompatibility complex (MHC-independent manner, consequently leading to the activation of antitumor function. The recent studies have confirmed that a variety of tumor-associated antigens (TAAs can act as target antigens for CAR-T cells. Nowadays, CAR T-cell therapy, one of the most potential tumor immunotherapies, has made great breakthroughs in hematological malignancies and promising outcomes in solid tumors. In this article, the biological characteristics and antitumor mechanism of CAR-T cells, and their application in tumor treatment were mainly reviewed.

  3. Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils

    DEFF Research Database (Denmark)

    Tovar, Cesar; Pye, Ruth J; Kreiss, Alexandre

    2017-01-01

    Devil facial tumour disease (DFTD) is a transmissible cancer devastating the Tasmanian devil (Sarcophilus harrisii) population. The cancer cell is the 'infectious' agent transmitted as an allograft by biting. Animals usually die within a few months with no evidence of antibody or immune cell...... responses against the DFTD allograft. This lack of anti-tumour immunity is attributed to an absence of cell surface major histocompatibility complex (MHC)-I molecule expression. While the endangerment of the devil population precludes experimentation on large experimental groups, those examined in our study...... indicated that immunisation and immunotherapy with DFTD cells expressing surface MHC-I corresponded with effective anti-tumour responses. Tumour engraftment did not occur in one of the five immunised Tasmanian devils, and regression followed therapy of experimentally induced DFTD tumours in three Tasmanian...

  4. Effectiveness of allergen-specific immunotherapy with pollen allergens in children from the viewpoint of molecular allergology

    Directory of Open Access Journals (Sweden)

    S.M. Nedelska

    2017-03-01

    , allergic rhinitis is complicated by sinusitis in 13 % of cases. Children received 3 to 4 courses of preseason subcutaneous ASIT (December to May according to classic scheme. The vast majority of children got mixed extracts of ragweed, cyclachaena, mugwort, quinoa, sunflower (90 %. One allergen (ragweed or sunflower has been used only in 6 children (10 %. We detected that 1/5 children had no clinical effect, the symptoms of hay fever were not diminished or changed their temporal frames. 82 % of patients without effect of ASIT had cross plant-food allergy (oral allergy syndrome. Conclusion. Before the beginning of АSІТ in children with hay fever, the doctor must define a high-risk group in relation to its possible ineffectiveness. We suggest taking into account children with sensitization to 4 and more pollen allergens, with the presence of oral allergic syndrome, concomitant pathology of ENT organs, in particular, adenoid hypertrophy, chronic sinusitis. Such children are recommended to make a profile of molecular allergy diagnostics to determine the specific immunoglobulines Е to the major and minor allergens. Component resolved molecular allergy diagnostics maybe also helpful in estimation the risk of systemic (anaphylactic reactions in children with cross reactivity (pollen-food allergy and in improvement of preventive measures, in particular, in patients with oral allergy syndrome.

  5. 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)

  6. 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

  7. 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.

  8. 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...

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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...

  3. 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.

  4. Conclusiveness of the Cochrane reviews in gynaecological cancer: A systematic analysis.

    Science.gov (United States)

    Yin, Shande; Chuai, Yunhai; Wang, Aiming; Zhang, Lanmei

    2015-06-01

    To assess the conclusiveness of Cochrane reviews in the field of gynaecological cancer. The Cochrane Library was searched for reviews regarding gynaecological cancer published between 1 January 2000 and 1 November 2014. Data were extracted from each paper and the conclusiveness of each review was assessed. The study included 66 reviews, 41 (62.1%) of which were conclusive. Of these, 58 included randomized controlled trials (RCTs), 37 (63.8%) of which were conclusive. Conclusive reviews of RCTs included significantly more patients than inconclusive reviews, but there was no difference in the number of included studies. Of the eight reviews of nonrandomized studies, four (50.0%) were conclusive. The majority of reviews recognized the need for additional studies. In the field of gynaecological cancer, reviews are more likely to be conclusive when they include RCTs, as well as large numbers of patients. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  5. Major Links.

    Science.gov (United States)

    Henderson, Tona

    1995-01-01

    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  6. Major Roads

    Data.gov (United States)

    Minnesota Department of Natural Resources — This data set contains roadway centerlines for major roads (interstates and trunk highways) found on the USGS 1:24,000 mapping series. These roadways are current...

  7. CSNI/NEA Rasplav seminar 2000. Summary and conclusions

    International Nuclear Information System (INIS)

    2001-01-01

    various boundary conditions were investigated. The work involved a combination of integral and separate effect tests including molten-salt tests to investigate non-eutectic mixtures and the effects of stratification, extension of the material property database to allow interpretation and modelling of the experimental data. The CSNI decided to hold a seminar where the major outcome of the RASPLAV Project could be presented and discussed also in the context of other experienced activities on Severe Accidents. The objectives of the seminar are: - to review the experimental results of the RASPLAV Project; - to exchange information on complementary research; - to discuss the progress made on understanding severe accident progression; - to discuss the applicability to nuclear power plants and use of the results. The Seminar was intended to provide an in-depth review of the RASPLAV Project in terms of the technical capabilities, results and analyses produced during the project execution. The application of the results and their significance for power plant applications were addressed. Relevant results of the complementary research carried out at various laboratories were also presented. The seminar consisted of five sessions organised as follows: - Opening and overview; - Experimental results; - Theoretical Analyses; - Application and complementary research; - Conclusion

  8. CSNI/NEA Rasplav seminar 2000. Summary and conclusions

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-01-15

    various boundary conditions were investigated. The work involved a combination of integral and separate effect tests including molten-salt tests to investigate non-eutectic mixtures and the effects of stratification, extension of the material property database to allow interpretation and modelling of the experimental data. The CSNI decided to hold a seminar where the major outcome of the RASPLAV Project could be presented and discussed also in the context of other experienced activities on Severe Accidents. The objectives of the seminar are: - to review the experimental results of the RASPLAV Project; - to exchange information on complementary research; - to discuss the progress made on understanding severe accident progression; - to discuss the applicability to nuclear power plants and use of the results. The Seminar was intended to provide an in-depth review of the RASPLAV Project in terms of the technical capabilities, results and analyses produced during the project execution. The application of the results and their significance for power plant applications were addressed. Relevant results of the complementary research carried out at various laboratories were also presented. The seminar consisted of five sessions organised as follows: - Opening and overview; - Experimental results; - Theoretical Analyses; - Application and complementary research; - Conclusion.

  9. Sublingual versus subcutaneous immunotherapy: patient adherence at a large German allergy center

    Directory of Open Access Journals (Sweden)

    Lemberg M

    2017-01-01

    Full Text Available Marie-Luise Lemberg,1 Till Berk,2 Kija Shah-Hosseini,1 Elena-Manja Kasche,1,3 Ralph Mösges1 1Faculty of Medicine, Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany; 2Department of Trauma Surgery, University Hospital Zurich, Zurich, Switzerland; 3Center for Dermatology, Specific Allergology and Environmental Medicine, Hamburg, Germany Background: Many placebo-controlled studies have demonstrated that allergen immunotherapy (AIT is an effective therapy for treating allergies. Both commonly used routes, subcutaneous (SCIT and sublingual immunotherapy (SLIT, require high patient adherence to be successful. In the literature, numbers describing adherence vary widely; this investigation compares these two routes of therapy directly.Methods: All data were retrieved from the patient data management system of a center for dermatology, specific allergology, and environmental medicine in Germany. All 330 patients (aged 13–89 years included in this study had commenced AIT between 2003 and 2011, thus allowing a full 3-year AIT cycle to be considered for each investigated patient.Results: In this specific center, SCIT was prescribed to 62.7% and SLIT to 37.3% of all included patients. The total dropout rate of the whole patient cohort was 34.8%. Overall, SLIT patients showed a higher dropout rate (39.0% than did SCIT patients (32.4%; however, the difference between these groups was not significant. Also, no significant difference between the overall dropout rates for men and for women was observed. A Kaplan–Meier curve of the patient collective showed a remarkably high dropout rate for the first year of therapy.Conclusion: The analysis presented in this single-center study shows that most patients who discontinue AIT do so during the first year of therapy. Patients seem likely to finish the 3-year therapy cycle if they manage to adhere to treatment throughout the first year. Strategies for preventing

  10. Spectrum of allergens for Japanese cedar pollinosis and impact of component-resolved diagnosis on allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Takashi Fujimura

    2015-10-01

    Full Text Available The high prevalence of Japanese cedar pollinosis in Japan is associated with a negative impact on the quality of life of patients, as well as significant loss of productivity among the workforce in early spring, thus representing a serious social problem. Furthermore, the prevalence is increasing, and has risen by more than 10% in this decade. Cry j 1 and Cry j 2 were identified as the major allergens in Japanese cedar pollen (JCP, and in 2004, the existence of other major and minor allergens were revealed by a combination of two-dimensional electrophoresis and immunoblotting analysis. Allergenome analysis identified a chitinase, a lipid transfer protein, a serine protease, and an aspartic protease as novel IgE-reactive allergens in patients with JCP allergy. Thaumatin-like protein (Cry j 3 was shown to be homologous to Jun a 3, a major allergen from mountain cedar pollen. Isoflavone reductase-like protein was also characterized in a study of a JCP cDNA library. The characterization of component allergens is required to clarify the sensitizer or cross-reactive elicitor allergens for component-resolved diagnosis (CRD. Increasing evidence from numerous clinical trials indicates that CRD can be used to design effective allergen-specific immunotherapy. In this review, we summarize the eight characterized JCP allergens and discuss the impact of CRD and characterization of novel allergens on allergen-specific immunotherapy.

  11. 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...

  12. Specific immunotherapy effect on peripheral blood T1/T2 lymphocytes in atopic patients

    Directory of Open Access Journals (Sweden)

    Manuela Rebordão

    2006-03-01

    Full Text Available Allergen-specific immunotherapy has been used for successful treatment of atopic diseases. They may act by modifying the patterns of cytokines produced by T cells. However, the precise mechanism by which it accomplishes these effects is still incompletely understood. Objective: To evaluate the effect of one year immunotherapy on cytokines profiles T1 and T2 of peripheral blood lymphocytes in atopic patients. Methods: We studied 10 atopic patients sensitised to common environmental allergens receiving immunotherapy over one year mean period. Six of these patients were studied before and after immunotherapy. Fourteen atopic patients untreated and 7 non-atopic subjects were used as control groups. Intracellular cytokine production (IFN-γ; IL-4; IL- 5; IL-10 was determined by flow cytometry following stimulation with phorbol myristate acetate (PMA, ionomycin and brefeldin. Mann-Whitney U and Wilcoxon non-parametric tests were utilized for the statistical analysis. Results: The expression of IL-4 and IL-5 in T cells, characteristically increased in atopic patients, respectively 13.8 (3.1 – 31.8 and 6.7% (1.0 -20.4, was significantly lower in the immunotherapy group 5.4 (2.9 -15.6 p=0.007 and 2.1% (0,6 – 4.8 p=0.035 and similar in the non-atopic control group. The levels of IFN-γ did not differ between the studied groups but the ratio IFN-γ / IL-4 produced by CD4+ T lymphocytes increased significantly in the patients receiving immunotherapy. In addition, there was an increase in the expression of IL-10 by T cells of the immunotherapy group compared to the non-atopic controls 1.9 (1.0 – 4.9 versus 1.4% (0.9 – 1.4 p=0.02, being more evident in CD8+ T lymphocytes. IL-10 correlated significantly with all the profile T2 cytokines (IL-4 and IL-5 and with the phenotype Tc2. Conclusion: After one year of immunotherapy the peripheral T cells response to a polyclonal stimulation revealed a reduction in IL-4 and IL-5 production

  13. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Felix Hart

    2017-05-01

    Full Text Available IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich and hematological (CD20 cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated.

  14. Tumor Cell-Free DNA Copy Number Instability Predicts Therapeutic Response to Immunotherapy.

    Science.gov (United States)

    Weiss, Glen J; Beck, Julia; Braun, Donald P; Bornemann-Kolatzki, Kristen; Barilla, Heather; Cubello, Rhiannon; Quan, Walter; Sangal, Ashish; Khemka, Vivek; Waypa, Jordan; Mitchell, William M; Urnovitz, Howard; Schütz, Ekkehard

    2017-09-01

    Purpose: Chromosomal instability is a fundamental property of cancer, which can be quantified by next-generation sequencing (NGS) from plasma/serum-derived cell-free DNA (cfDNA). We hypothesized that cfDNA could be used as a real-time surrogate for imaging analysis of disease status as a function of response to immunotherapy and as a more reliable tool than tumor biomarkers. Experimental Design: Plasma cfDNA sequences from 56 patients with diverse advanced cancers were prospectively collected and analyzed in a single-blind study for copy number variations, expressed as a quantitative chromosomal number instability (CNI) score versus 126 noncancer controls in a training set of 23 and a blinded validation set of 33. Tumor biomarker concentrations and a surrogate marker for T regulatory cells (Tregs) were comparatively analyzed. Results: Elevated CNI scores were observed in 51 of 56 patients prior to therapy. The blinded validation cohort provided an overall prediction accuracy of 83% (25/30) and a positive predictive value of CNI score for progression of 92% (11/12). The combination of CNI score before cycle (Cy) 2 and 3 yielded a correct prediction for progression in all 13 patients. The CNI score also correctly identified cases of pseudo-tumor progression from hyperprogression. Before Cy2 and Cy3, there was no significant correlation for protein tumor markers, total cfDNA, or surrogate Tregs. Conclusions: Chromosomal instability quantification in plasma cfDNA can serve as an early indicator of response to immunotherapy. The method has the potential to reduce health care costs and disease burden for cancer patients following further validation. Clin Cancer Res; 23(17); 5074-81. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. 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.)

  16. 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.)

  17. Hypothesis, Prediction, and Conclusion: Using Nature of Science Terminology Correctly

    Science.gov (United States)

    Eastwell, Peter

    2012-01-01

    This paper defines the terms "hypothesis," "prediction," and "conclusion" and shows how to use the terms correctly in scientific investigations in both the school and science education research contexts. The scientific method, or hypothetico-deductive (HD) approach, is described and it is argued that an understanding of the scientific method,…

  18. Conclusion Chapters in Doctoral Theses: Some International Findings

    Science.gov (United States)

    Trafford, Vernon; Leshem, Shosh; Bitzer, Eli

    2014-01-01

    This study investigated how candidates claimed to have made an original contribution to knowledge in the conclusion chapters of 100 PhD theses. Documentary analysis was used to discover how this was explained within theses at selected universities in three countries. No other documents were accessed and neither were candidates, supervisors or…

  19. Overview of human health in the Arctic: conclusions and recommendations.

    Science.gov (United States)

    Donaldson, Shawn; Adlard, Bryan; Odland, Jon Øyvind

    2016-01-01

    This article is intended to provide an overview of the key conclusions, knowledge gaps and key recommendations based on the recent 2015 Arctic human health assessment under the Arctic Monitoring and Assessment Program. This assessment was based primarily on data from human health monitoring and research studies and peer-reviewed literature published since the last assessment in 2009.

  20. 20 CFR 901.48 - Proposed findings and conclusions.

    Science.gov (United States)

    2010-04-01

    ... Law Judge, before making his/her decision, shall give the parties a reasonable opportunity to submit... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Proposed findings and conclusions. 901.48 Section 901.48 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE...

  1. Actual Problems of Conclusion and Discharge of Urgent Labour Contracts

    Directory of Open Access Journals (Sweden)

    Shevelyova A. A.

    2013-05-01

    Full Text Available This article is devoted to the consideration of the questions connected with the conclusion and the termination of the urgent labour contract. The author, analyzing judicial practice, allocates the problems of separate regulation of the RF labour legislation enforcement.

  2. Debris impact on emergency coolant recirculation - summary and conclusions

    International Nuclear Information System (INIS)

    Jain, Bhagwat; Hsia, Anthony; Armand, Yves; Mattei, Jean-Marie; Hyvaerinen, Juhani; Maqua, Michael; Puetter, Bernhard; Sandervaag, Oddbjoern; Vandewalle, Andre; Tombuyses, Beatrice; Pyy, Pekka; Royen, Jacques

    2004-01-01

    to two orders of magnitude because of strainer clogging. Consequently, the CSNI decided to continue its previous efforts in the area. The overall purpose of the 2004 Workshop was to discuss the impact of new information made available since 1996 and to promote consensus among member countries on identification of remaining technical issues important to safety, and on possible paths for their resolution. The specific purposes of the Workshop were: a. To review the knowledge base and in particular information developed after 1999, and to consider the validity of the conclusions drawn. b. To exchange information on the current status of research related to debris generation, debris transportation, and sump strainer clogging and penetration phenomena, in particular for PWRs, and to assess uncertainties. c. To exchange and disseminate information on recent and current activities and practices in these areas. d. To identify and discuss differences between approaches relevant to reactor safety. e. To identify technical issues and programs of interest for international collaborative research and develop an Action Plan outlining activities that CSNI should undertake in the area of strainer or sump screen clogging during the next few years. Summary of the main findings: a. The safety significance of the sump strainer clogging depends on the plant design (e.g. sump strainer, ECCS) and backfitting measures performed. b. The following are examples of PWR design features that could influence the debris impact on the ECCS sump performance: - Type of insulation (material, combination of materials, protection). - Break size to be postulated. - Transport in containment with or without containment spray system (CSS). - Degree of turbulence and flow velocities in the sump influenced by CSS, water level, break flow location and sump geometry. - Redundancy of sumps and residual heat removal system (RHRS). - Strainer design (area, mesh size). - Positioning of recirculation pumps and vortex

  3. 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.

  4. An enhanced heterologous virus-like particle for human papillomavirus type 16 tumour immunotherapy.

    Directory of Open Access Journals (Sweden)

    Khairunadwa Jemon

    Full Text Available Cervical cancer is caused by high-risk, cancer-causing human papillomaviruses (HPV and is the second highest cause of cancer deaths in women globally. The majority of cervical cancers express well-characterized HPV oncogenes, which are potential targets for immunotherapeutic vaccination. Here we develop a rabbit haemorrhagic disease virus (RHDV virus-like particle (VLP-based vaccine designed for immunotherapy against HPV16 positive tumours. An RHDV-VLP, modified to contain the universal helper T cell epitope PADRE and decorated with an MHC I-restricted peptide (aa 48-57 from the HPV16 E6, was tested for its immunotherapeutic efficacy against the TC-1 HPV16 E6 and E7-expressing tumour in mice. The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25 or to block T cell suppression mediated through CTLA-4. As a result, the tumour burden was reduced by around 50% and the median survival time of mice to the humane endpoint was almost doubled the compared to controls. The incorporation of PADRE into the RHDV-VLP was necessary for an E6-specific enhancement of the anti-tumour response and the co-administration of the immune modifying antibodies contributed to the overall efficacy of the immunotherapy. The E6-RHDV-VLP-PADRE shows immunotherapeutic efficacy, prolonging survival for HPV tumour-bearing mice. This was enhanced by the systemic administration of immune-modifying antibodies that are commercially available for use in humans. There is potential to further modify these particles for even greater efficacy in the path to development of an immunotherapeutic treatment for HPV precancerous and cancer stages.

  5. A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy.

    Science.gov (United States)

    Swoboda, Ines; Bugajska-Schretter, Agnes; Linhart, Birgit; Verdino, Petra; Keller, Walter; Schulmeister, Ulrike; Sperr, Wolfgang R; Valent, Peter; Peltre, Gabriel; Quirce, Santiago; Douladiris, Nikolaos; Papadopoulos, Nikolaos G; Valenta, Rudolf; Spitzauer, Susanne

    2007-05-15

    IgE-mediated allergy to fish is a frequent cause of severe anaphylactic reactions. Parvalbumin, a small calcium-binding protein, is the major fish allergen. We have recently isolated a cDNA coding for carp parvalbumin, Cyp c 1, and expressed in Escherichia coli a recombinant Cyp c 1 molecule, which contained most IgE epitopes of saltwater and freshwater fish. In this study, we introduced mutations into the calcium-binding domains of carp parvalbumin by site-directed mutagenesis and produced in E. coli three parvalbumin mutants containing amino acid exchanges either in one (single mutants; Mut-CD and Mut-EF) or in both of the calcium-binding sites (double mutant; Mut-CD/EF). Circular dichroism analyses of the purified derivatives and the wild-type allergen showed that Mut-CD/EF exhibited the greatest reduction of overall protein fold. Dot blot assays and immunoblot inhibition experiments performed with sera from 21 fish-allergic patients showed that Mut-CD/EF had a 95% reduced IgE reactivity and represented the derivative with the least allergenic activity. The latter was confirmed by in vitro basophil histamine release assays and in vivo skin prick testing. The potential applicability for immunotherapy of Mut-CD/EF was demonstrated by the fact that mouse IgG Abs could be raised by immunization with the mutated molecule, which cross-reacted with parvalbumins from various fish species and inhibited the binding of fish-allergic patients' IgE to the wild-type allergen. Using the hypoallergenic carp parvalbumin mutant Mut-CD/EF, it may be possible to treat fish allergy by immunotherapy.

  6. Cosmological Gamma-Ray Bursts and Hypernovae Conclusively Linked

    Science.gov (United States)

    2003-06-01

    -ray radiation. The team concludes that it is likely to be due to the nearly instantaneous, non-symmetrical collapse of the inner region of a highly developed star (known as the "collapsar" model) . The March 29 gamma-ray burst will pass into the annals of astrophysics as a rare "type-defining event", providing conclusive evidence of a direct link between cosmological gamma-ray bursts and explosions of very massive stars . PR Photo 17a/03 : Image of the optical afterglow of GRB 030329 (VLT FORS1+2). PR Photo 17b/03 : A series of VLT spectra of the optical afterglow of GRB 030329. What are Gamma-Ray Bursts? One of the currently most active fields of astrophysics is the study of the dramatic events known as "gamma-ray bursts (GRBs)" . They were first detected in the late 1960's by sensitive instruments on-board orbiting military satellites, launched for the surveillance and detection of nuclear tests. Originating, not on the Earth, but far out in space, these short flashes of energetic gamma-rays last from less than a second to several minutes. Despite major observational efforts, it is only within the last six years that it has become possible to pinpoint with some accuracy the sites of some of these events. With the invaluable help of comparatively accurate positional observations of the associated X-ray emission by various X-ray satellite observatories since early 1997, astronomers have until now identified about fifty short-lived sources of optical light associated with GRBs (the "optical afterglows"). Most GRBs have been found to be situated at extremely large ("cosmological") distances. This implies that the energy released in a few seconds during such an event is larger than that of the Sun during its entire lifetime of more than 10,000 million years. The GRBs are indeed the most powerful events since the Big Bang known in the Universe, cf. ESO PR 08/99 and ESO PR 20/00 . During the past years circumstantial evidence has mounted that GRBs signal the collapse of massive

  7. 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

  8. 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.

  9. 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.

  10. 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)

  11. 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

  12. 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....

  13. Conclusion: imaging in strategy of endocrine diagnosis and therapeutics

    International Nuclear Information System (INIS)

    Mornex, R.

    1995-01-01

    Images in medicine have to help the doctor in a diagnostic or therapeutic aim. The choice must be made in function of pathology or organ as known (it is not necessary to ask for a computed tomography where we know that only an echography can give the answer to the question we ask ), the criteria must stay the best performance for the cheapest price, but the quality of interpretation is a more important thing. It is important to avoid a lot of examinations which do not give better informations but are heavy to endure for the patients. In conclusion, the aim of this kind of proceedings is to assure to the patients who come confidently to us, the best service at the less constraints price without forgetting that a conclusion depends on a given methodological situation and reminding of beside machines we have not to forget the men

  14. Conclusive identification of quantum channels via monogamy of quantum correlations

    International Nuclear Information System (INIS)

    Kumar, Asutosh; Singha Roy, Sudipto; Pal, Amit Kumar; Prabhu, R.; Sen, Aditi; Sen, Ujjwal

    2016-01-01

    We investigate the action of global noise and local channels, namely, amplitude-damping, phase-damping, and depolarizing channels, on monogamy of quantum correlations, such as negativity and quantum discord, in three-qubit systems. We discuss the monotonic and non-monotonic variation, and robustness of the monogamy scores. By using monogamy scores, we propose a two-step protocol to conclusively identify the noise applied to the quantum system, by using generalized Greenberger–Horne–Zeilinger and generalized W states as resource states. We discuss a possible generalization of the results to higher number of parties. - Highlights: • Monogamy score monotonically decays with noise for generalized GHZ state as input. • Non-monotonically decaying monogamy score with noise for generalized W state as input. • Characterizing the dynamics of monogamy score. • Dynamics terminal quantifying robustness of monogamy score against noise. • Conclusively identifying the type of noise using monogamy score.

  15. Conclusive identification of quantum channels via monogamy of quantum correlations

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Asutosh; Singha Roy, Sudipto; Pal, Amit Kumar [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211019 (India); Homi Bhaba National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India); Prabhu, R. [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211019 (India); Homi Bhaba National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India); Department of Physics, Indian Institute of Technology Patna, Bihta 801103, Bihar (India); Sen, Aditi, E-mail: aditi@hri.res.in [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211019 (India); Homi Bhaba National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India); Sen, Ujjwal [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211019 (India); Homi Bhaba National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India)

    2016-10-23

    We investigate the action of global noise and local channels, namely, amplitude-damping, phase-damping, and depolarizing channels, on monogamy of quantum correlations, such as negativity and quantum discord, in three-qubit systems. We discuss the monotonic and non-monotonic variation, and robustness of the monogamy scores. By using monogamy scores, we propose a two-step protocol to conclusively identify the noise applied to the quantum system, by using generalized Greenberger–Horne–Zeilinger and generalized W states as resource states. We discuss a possible generalization of the results to higher number of parties. - Highlights: • Monogamy score monotonically decays with noise for generalized GHZ state as input. • Non-monotonically decaying monogamy score with noise for generalized W state as input. • Characterizing the dynamics of monogamy score. • Dynamics terminal quantifying robustness of monogamy score against noise. • Conclusively identifying the type of noise using monogamy score.

  16. Review conclusions by Ernst and Canter regarding spinal manipulation refuted

    Directory of Open Access Journals (Sweden)

    Evans Roni

    2006-08-01

    Full Text Available Abstract In the April 2006 issue of the Journal of Royal Society of Medicine, Ernst and Canter authored a review of the most recent systematic reviews on the effectiveness of spinal manipulation for any condition. The authors concluded that, except for back pain, spinal manipulation is not an effective intervention for any condition and, because of potential side effects, cannot be recommended for use at all in clinical practice. Based on a critical appraisal of their review, the authors of this commentary seriously challenge the conclusions by Ernst and Canter, who did not adhere to standard systematic review methodology, thus threatening the validity of their conclusions. There was no systematic assessment of the literature pertaining to the hazards of manipulation, including comparison to other therapies. Hence, their claim that the risks of manipulation outweigh the benefits, and thus spinal manipulation cannot be recommended as treatment for any condition, was not supported by the data analyzed. Their conclusions are misleading and not based on evidence that allow discrediting of a large body of professionals using spinal manipulation.

  17. 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

  18. Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract

    DEFF Research Database (Denmark)

    Schmid, Johannes Martin; Würtzen, Peter Adler; Dahl, Ronald

    2016-01-01

    BACKGROUND: Allergen immunotherapy is an effective treatment of allergic rhinoconjunctivitis. Clinical efficacy is associated with improvement of basophil sensitivity and an increase in allergen-specific immunoglobulin concentration. OBJECTIVE: We sought to determine whether changes in allergen...... component-specific serum IgE and IgG4 levels during the updosing phase of subcutaneous immunotherapy (SCIT) are biomarkers of the immunologic changes that can lead to treatment efficacy. METHODS: Twenty-four subjects with grass pollen-induced allergic rhinoconjunctivitis were randomized 3:1 to receive SCIT...... (Alutard SQ) or to an open control group. IgE and IgG4 concentrations were determined for the major allergens Phl p 1 or Phl p 5 by using ImmunoCAP and for 8 grass pollen molecules by using Immuno Solid-phase Allergy Chip (ISAC) before treatment and after updosing. RESULTS: Levels of specific IgE against...

  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. 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.

  3. 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.

  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. Allergenspecific Immunotherapy: History, Current Views and Problems

    Directory of Open Access Journals (Sweden)

    M.I. Derkach

    2013-09-01

    Monitoring of patients who are allergic pathology, Western regional center of clinical immunology and allergology 10 years have shown that the number of IgE-dependent diseases accounted for 72.3 % of the total surveyed 5845 patients. The vast majority of patients were suffering from hay fever — 91.8 %, allergic rhinosinusitis — 84.7 %, atopic dermatitis — 70.2 %, asthma — 58.6 %, urticaria — 54.8 %, other IgE-dependent diseases/response — 50.8 %. Conducting allergenspecific diagnosis identified the need for SIT and ASIT. Unfortunately, the percentage of patients who received this type of therapy was only 5.3 %. The reasons for this low level of this type of treatment a lot, and in modern terms with the need of a wider study allergist and the patients to change their attitude towards the use of SIT and ASIT especially as evidence of treatment IgE-dependent allergic diseases with level of evidence A.

  10. Merkel Cell Carcinoma: An Update and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Hiroshi Uchi

    2018-03-01

    Full Text Available Merkel cell carcinoma (MCC is a rare but aggressive skin cancer with frequent metastasis and death. MCC has a mortality rate of 30%, making it more lethal than malignant melanoma, and incidence of MCC has increased almost fourfold over the past 20 years in the USA. MCC has long been considered to be an immunogenic cancer because it occurs more frequently in immunosuppressed patients from organ transplant and HIV infection than in those with immunocompetent. Chronic UV light exposure and clonal integration of Merkel cell polyomavirus (MCPyV are two major causative factors of MCC. Approximately 80% of MCC are associated with MCPyV, and T cells specific for MCPyV oncoproteins are present in the blood and tumors of patients. Several studies have shown that a subset of MCCs express PD-1 on tumor-infiltrating lymphocytes and express PD-L1 on tumor cells, which suggests an endogenous tumor-reactive immune response that might be unleashed by anti-PD-1 or anti-PD-L1 drugs.

  11. Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology.

    Science.gov (United States)

    Kalos, Michael; June, Carl H

    2013-07-25

    Adoptive T cell transfer for cancer and chronic infection is an emerging field that shows promise in recent trials. Synthetic-biology-based engineering of T lymphocytes to express high-affinity antigen receptors can overcome immune tolerance, which has been a major limitation of immunotherapy-based strategies. Advances in cell engineering and culture approaches to enable efficient gene transfer and ex vivo cell expansion have facilitated broader evaluation of this technology, moving adoptive transfer from a "boutique" application to the cusp of a mainstream technology. The major challenge currently facing the field is to increase the specificity of engineered T cells for tumors, because targeting shared antigens has the potential to lead to on-target off-tumor toxicities, as observed in recent trials. As the field of adoptive transfer technology matures, the major engineering challenge is the development of automated cell culture systems, so that the approach can extend beyond specialized academic centers and become widely available. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. It pays to be green. A premature conclusion?

    International Nuclear Information System (INIS)

    Telle, K.

    2006-01-01

    It has been claimed that good environmental performance can improve firms' economic performance. However, because of e.g. data limitations, the methods applied in most previous quantitative empirical studies on effects of environmental performance on economic performance of firms suffer from several shortcomings. We discuss these shortcomings and conclude that previously applied methods are unsatisfactory as support for a conclusion that it pays for firms to be green. Then we illustrate the consequences of these shortcomings by performing several regression analyses of the effect of environmental performance on economic performance using a panel data set of Norwegian plants. A pooled regression where observable firm characteristics like e.g. size or industry are controlled for, confirms a positive effect of environmental performance on economic performance. However, the estimated positive effect could be due to omitted unobserved variables like management or technology. When the regression model controls for unobserved plant heterogeneity, the effect is generally no longer statistically significant. Hence, although greener plants tend to perform economically better, the analysis provides little support for the claim that it is because they are greener. These empirical findings further indicate that a conclusion that it pays to be green is premature

  13. [Immunotherapy for renal cell carcinoma - current status].

    Science.gov (United States)

    Grimm, Marc-Oliver; Foller, Susan

    2018-04-01

    Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo ® ) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard ratio 0.73; p = 0.0006) and response rate (26 % vs. 5 %) as well as a favorable toxicity profile compared with Everolimus. Currently, numerous combinations with PD-1/PD-L1 inhibitors are compared to Sunitinib as first line treatment of mRCC. Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42 % vs. 27 %, p < 0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo + Ipi has been not yet reached (28.2 - NR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients. Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib. However, a considerable increase of immune related adverse events is associated with the immune combination therapy. Another randomized trial demonstrates improved progression-free survival for the combination of the PD-L1 inhibitor Atezolizumab and the VEGF antibody Bevacizumab in patients with PD-L1 positive tumors; this was found in all IMDC risk groups. Further phase-3 trials with "new" VEGFR-TKIs (Axitinib, Cabozantinib, Lenvatinib) and PD-1/PD-L1 inhibitor combinations are ongoing.In conclusion, the PD-1 immune checkpoint inhibitor Nivolumab will remain a standard treatment for patients with metastatic renal cell carcinoma

  14. Clinical Aspects of Using of Etiotropic Immunotherapy in Complex Treatment of Patients with Acute Optic Neuritis Associated with Herpesvirus Infection

    Directory of Open Access Journals (Sweden)

    D. A. Povaliaeva

    2018-01-01

    Full Text Available Purpose. To study the clinical effectiveness of the system of complex treatment of optic neuritis (ON associated with herpesvirus infection(HVI, including methods of immunopharmacotherapy. Patients and methods. The clinical study involved 55 people (55 eyes with acuteON associated with HVI. The treatment regimen for all patients included 10 days the addition of Dexamethasone solution to optic nerve on decreasing scheme, Emoxypine 1% 0.5 ml, and Dicynone 12.5% 0.5 ml through irrigation system implanted in retrobulbar space, in combination with appoint of neuroprotective drugs (Picamilon and Semax. Depending on features of immunotherapy, all patients were divided into 3 groups. The first group consisted of 20 patients, whose treatment in addition to the above included intravenously infusions 6 mg of Polyoxidonium from the moment they entered the eye hospital. The second group included 17 patients who received in addition to Polyoxidonium, muscle injections of Cycloferon, in mode and doses according to the manufacturer's instructions. The third group of patients (18 peoples — with using etiotropic immunotherapy that consisted of combination of Polyoxidonium, Cycloferon and endonasal electrophoresis of 0.25% solution of Derinat. The duration of immunotherapy was 10–12 days. Results. The analysis of obtained datas showed that more significant positive dynamics was noted in the clinical course of ON in patients of the 3rd group of observation, who simultaneously received complex of 3 immunotropic drugs in comparison with group 1 and 2, in the treatment of which we used one immunotropic drug Polyoxidonium, or its combination with Cycloferon, without Derinat. Conclusions. The method of etiotropic and pathogenetic immunotherapy developed by us, represented by the combination of Polyoxidonium, Cycloferon and Derinat, at ON, associated with herpesvirus infection, allows to shorten by 2 times or more the period of stopping of signs of

  15. Conclusion of the I.C.T. benchmark exercise

    International Nuclear Information System (INIS)

    Giacometti, A.

    1991-01-01

    The ICT Benchmark exercise made within the RIV working group of ESARDA on reprocessing data supplied by COGEMA for 53 routines reprocessing input batches made of 110 irradiated fuel assemblies from KWO Nuclear Power Plant was finally evaluated. The conclusions are: all seven different ICT methods applied verified the operator data on plutonium within about one percent; anomalies intentionally introduced to the operator data were detected in 90% of the cases; the nature of the introduced anomalies, which were unknown to the participants, was completely resolved for the safeguards relevant cases; the false alarm rate was in a few percent range. The ICT Benchmark results shows that this technique is capable of detecting and resolving anomalies in the reprocessing input data to the order of a percent

  16. The European Food Consumption Validation Project: conclusions and recommendations

    DEFF Research Database (Denmark)

    de Boer, E. J.; Slimani, N.; van 't Veer, P.

    2011-01-01

    Background/Objectives: To outline and discuss the main results and conclusions of the European Food Consumption Validation (EFCOVAL) Project. Subjects/Methods: The EFCOVAL Project was carried out within the EU Sixth Framework Program by researchers in 11 EU countries. The activities focused on (1...... showed that two non-consecutive EPIC-Soft 24-HDRs are suitable to estimate the usual intake distributions of protein and potassium of European adult populations. The 2-day non-consecutive 24-HDRs in combination with a food propensity questionnaire also appeared to be appropriate to rank individuals...... according to their fish and fruit and vegetable intake in a comparable way in five European centers. Dietary intake of (young) children can be assessed by the combination of EPIC-Soft 24-HDRs and food recording booklets. The EPIC-Soft-standardized method of describing foods is useful to estimate dietary...

  17. The accident at the Harrisburg nuclear reactor - Interim conclusions

    International Nuclear Information System (INIS)

    Yiftah, S.

    1979-07-01

    This work describes the first minutes, first day and first week following the Three Mile Island accident. It shows the failures that occurred and the lessons which should be derived. It is pointed out that the doses of radiation that escaped from the TMI plant were at no time large enough to have had any effect on the 2 million people living on a radius of 80 km from the plant. Although no casualties occurred the Harrisburg accident will create an impulse for a new study and understanding of the nuclear plant safety and might serve as a live safety laboratory. After the TMI accident nuclear plants are already safer, one of the conclusions being that a new planning of the operation room is required, with the operators acquiring a better understanding of what is going on during a nuclear reactor accident. (B.G.)

  18. Workshop on large molten pool heat transfer summary and conclusions

    International Nuclear Information System (INIS)

    1994-01-01

    The CSNI Workshop on Large Molten Heat Transfer held at Grenoble (France) in March 1994 was organised by CSNI's Principal Working Group on the Confinement of Accidental Radioactive Releases (PWG4) with the cooperation of the Principal Working Group on Coolant System Behaviour (FWG2) and in collaboration with the Grenoble Nuclear Research Centre of the French Commissariat a l'Energie Atomique (CEA). Conclusions and recommendations are given for each of the five sessions of the workshops: Feasibility of in-vessel core debris cooling through external cooling of the vessel; Experiments on molten pool heat transfer; Calculational efforts on molten pool convection; Heat transfer to the surrounding water - experimental techniques; Future experiments and ex-vessel studies (open forum discussion)

  19. Jumping to conclusions and the continuum of delusional beliefs.

    Science.gov (United States)

    Warman, Debbie M; Lysaker, Paul H; Martin, Joel M; Davis, Louanne; Haudenschield, Samantha L

    2007-06-01

    The present study examined the jumping to conclusions reasoning bias across the continuum of delusional ideation by investigating individuals with active delusions, delusion prone individuals, and non-delusion prone individuals. Neutral and highly self-referent probabilistic reasoning tasks were employed. Results indicated that individuals with delusions gathered significantly less information than delusion prone and non-delusion prone participants on both the neutral and self-referent tasks, (preferent task (p=.002). Those with delusions and those who were delusion prone reported higher confidence in their performance on the self-referent task than they did the neutral task (p=.02), indicating that high self-reference impacted information processing for individuals in both of these groups. The results are discussed in relation to previous research in the area of probabilistic reasoning and delusions.

  20. Snakebites in French Guiana: Conclusions of an international symposium.

    Science.gov (United States)

    Kallel, Hatem; Hommel, Didier; Mehdaoui, Hossein; Megarbane, Bruno; Resiere, Dabor

    2018-05-01

    A workshop on epidemiology and management of snakebites in French Guiana was performed at Cayenne, French Guiana from September 15 to September 16, 2017, under the auspices of the French Regional Health Agency (ARS) and the Pan American Health Organization (PAHO). The activity was attended by experts from France (Angers, Martinique, French Guiana, Guadeloupe, and Paris), Costa Rica, Brazil, Saint Lucia, and Surinam. The epidemiology, clinical manifestations, clinical grading and the management of snakebite in French Guiana were discussed. The conclusions of this symposium illustrated the urgent need to ensure accessibility of effective and safe polyvalent viperid antivenom in French Guiana. Finally, the results of this symposium have forged ties based on mutual goals and objectives. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Conclusions regarding geotechnical acceptability of the WIPP site

    International Nuclear Information System (INIS)

    Weart, W.D.

    1983-01-01

    The Waste Isolation Pilot Plant (WIPP) was authorized by Congress in 1980 as an unlicensed research and development (R and D) facility to demonstrate the safe disposal of radioactive wastes arising from the defense activities and programs of the United States. WIPP is now being constructed in southeast New Mexico, using salt beds about 655 m below the surface of the ground. Construction of the full WIPP facility will not commence until a preliminary underground excavation phase, called Site and Preliminary Design Validation (SPDV), is satisfactorily concluded in the summer of 1983. This SPDV program permits confirmation of subsurface geology, in drifts at planned facility depth that extend for 1555 m in a north-south direction, and in the two vertical shafts that provide access to these drifts. The subsurface studies are nearing completion, and it is therefore appropriate to draw conclusions regarding the geotechnical acceptability of the WIPP site. Four geotechnical elements are discussed: dissolution, deformation, hydrologic regime, and natural resources

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Executive summary and general conclusions of the rock sealing project

    International Nuclear Information System (INIS)

    Pusch, R.

    1992-06-01

    The Stripa Rock Sealing Project logically followed the two first Stripa research phases dealing with canister-embedment and plugging of excavations in repositories. The major activities in the third phase were: * Literature review and interviews for setting the state of art of rock fracture sealing. * Pilot field and lab testing applying a new effective 'dynamic' grouting technique. * Development of a general grout flow theory. * Investigation of physical properties and longevity of major candidate grouts. * Performance of 4 large-scale tests. The literature study showed that longevity aspects limited the number of potentially useful grout materials to smectitic clay and cement. The pilot testing showed that fine-grained grouts can be effectively injected in relatively fine fractures. The theoretical work led to a general grout flow theory valid both for grouting at a constant, static pressure with non-Newtonian material properties, and for 'dynamic' injection with superimposed oscillations, yielding Newtonian material behavior. The investigation of physical properties of candidate grouts with respect to hydraulic conductivity, shear strength, sensitivity to mechanical strain, as well as to chemical stability, showed that effective sealing is offered, and that any rock can have its bulk conductivity reduced to about 10 -10 m/s. The field tests comprised investigation of excavation-induced disturbance and attempts to seal disturbed rock, and in separate tests, grouting of deposition holes and a natural fine-fracture zone. Considerable disturbance of nearfield rock by blasting and stress changes, yielding an increase in axial hydraulic conductivity by 3 and 1 order of magnitude, respectively, was documented but various factors, primarily debris in the fractures, made grouting of blasted rock ineffective. Narrow fractures in deposition holes and in a natural fracture zone were sealed rather effectively. (au)

  18. First successful case of in vitro fertilization-embryo transfer with venom immunotherapy for hymenoptera sting allergy

    Directory of Open Access Journals (Sweden)

    Tucker Michael J

    2004-10-01

    Full Text Available Abstract Background To describe immune and endocrine responses in severe hymenoptera hypersensitivity requiring venom immunotherapy (VIT during in vitro fertilization (IVF. Case presentation A 39-year old patient was referred for history of multiple miscarriage and a history of insect sting allergy. Four years earlier, she began subcutaneous injection of 100 mcg mixed vespid hymenoptera venom/venom protein every 5–6 weeks. The patient had one livebirth and three first trimester miscarriages. Allergy treatment was maintained for all pregnancies ending in miscarriage, although allergy therapy was discontinued for the pregnancy that resulted in delivery. At our institution ovulation induction incorporated venom immunotherapy (VIT during IVF, with a reduced VIT dose when pregnancy was first identified. Serum IgE was monitored with estradiol during ovulation induction and early pregnancy. Response to controlled ovarian hyperstimulation was favorable while VIT was continued, with retrieval of 12 oocytes. Serum RAST (yellow jacket IgE levels fluctuated in a nonlinear fashion (range 36–54% during gonadotropin therapy and declined after hCG administration. A healthy female infant was delivered at 35 weeks gestation. The patient experienced no untoward effects from any medications during therapy. Conclusion Our case confirms the safety of VIT in pregnancy, and demonstrates RAST IgE can remain

  19. Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver.

    Science.gov (United States)

    Nemunaitis, John; Barve, Minal; Orr, Douglas; Kuhn, Joseph; Magee, Mitchell; Lamont, Jeffrey; Bedell, Cynthia; Wallraven, Gladice; Pappen, Beena O; Roth, Alyssa; Horvath, Staci; Nemunaitis, Derek; Kumar, Padmasini; Maples, Phillip B; Senzer, Neil

    2014-01-01

    Therapies for advanced hepatocellular carcinoma (HCC) are limited. We carried out a phase I trial of a novel autologous whole-cell tumor cell immunotherapy (FANG™), which incorporates a dual granulocyte macrophage colony-stimulating factor (GM-CSF) expressive/bifunctional small hairpin RNA interference (bi-shRNAi) vector. The bi-shRNAi DNA targets furin, which is a proconvertase of transforming growth factors beta (TGFβ) 1 and 2. Safety, mechanism, immunoeffectiveness, and suggested benefit were previously shown [Senzer et al.: Mol Ther 2012;20:679-689; Senzer et al.: J Vaccines Vaccin 2013;4:209]. We now provide further follow-up of a subset of 8 HCC patients. FANG manufacturing was successful in 7 of 8 attempts (one failure due to insufficient cell yield). Median GM-CSF expression was 144 pg/10(6) cells, TGFβ1 knockdown was 100%, and TGFβ2 knockdown was 93% of the vector-transported cells. Five patients were vaccinated (1 or 2.5×10(7) cells/intradermal injection, 6-11 vaccinations). No FANG toxicity was observed. Three of these patients demonstrated evidence of an immune response to the autologous tumor cell sample. Long-term follow-up demonstrated survival of 319, 729, 784, 931+, and 1,043+ days of the FANG-treated patients. In conclusion, evidence supports further assessment of the FANG immunotherapy in HCC. © 2014 S. Karger AG, Basel.

  20. Specific immunotherapy modifies allergen-specific CD4+ T cell responses in an epitope-dependent manner

    Science.gov (United States)

    Wambre, Erik; DeLong, Jonathan H.; James, Eddie A.; Torres-Chinn, Nadia; Pfützner, Wolfgang; Möbs, Christian; Durham, Stephen R.; Till, Stephen J.; Robinson, David; Kwok, William W.

    2014-01-01

    Background Understanding the mechanisms by which the immune system induces and controls allergic inflammation at the T cell epitope level is critical for the design of new allergy vaccine strategies. Objective To characterize allergen-specific T cell responses linked with allergy or peripheral tolerance and to determine how CD4+ T cell responses to individual allergen-derived epitopes change over allergen-specific immunotherapy (ASIT). Methods Timothy grass pollen (TGP) allergy was used as a model for studying grass pollen allergies. The breadth, magnitude, epitope hierarchy and phenotype of the DR04:01-restricted TGP-specific T cell responses in ten grass pollen allergic, five non-atopic and six allergy vaccine-treated individuals was determined using an ex vivo pMHCII-tetramer approach. Results CD4+ T cells in allergic individuals are directed to a broad range of TGP epitopes characterized by defined immunodominance hierarchy patterns and with distinct functional profiles that depend on the epitope recognized. Epitopes that are restricted specifically to either TH2 or TH1/TR1 responses were identified. ASIT was associated with preferential deletion of allergen-specific TH2 cells and without significant change in frequency of TH1/TR1 cells. Conclusions Preferential allergen-specific TH2-cells deletion after repeated high doses antigen stimulation can be another independent mechanism to restore tolerance to allergen during immunotherapy. PMID:24373351