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Sample records for anti-cd25 immunotherapy elicits

  1. RA8, A human anti-CD25 antibody against human treg cells

    Energy Technology Data Exchange (ETDEWEB)

    Arias, Robyn; Flanagan, Meg; Miller, Keith D.; Nien, Yu-Chih; Hu, Peisheng; Gray, Dixon; Khawli, Leslie A.; Epstein, Alan L.

    2007-06-01

    Although anti-CD25 antibodies exist for clinical use in patients, there is a need for the development of a human Treg antibody that will abrogate the immunosuppressive function of this small but critical T cell subtype. Based upon mounting evidence that the level of Treg cells in the tumor microenvironment correlates with clinical prognosis and stage in man, it appears that Treg cells play an important role in the tumor's ability to overcome host immune responses. In mice, the rat anti-mouse CD25 antibody PC61 causes depletion of CD25-bearing Treg cells both peripherally in lymphatic tissues and in the tumor microenvironment, without inducing symptoms of autoimmunity. A similar antibody, though with the ability to delete Treg cells specifically, would be an important new tool for reversing tumor escape associated with Treg immunosuppression in man. To begin to generate such a reagent, we now describe the development of a human anti-CD25 antibody using a novel yeast display library. The target antigen CD25-Fc was constructed and used for five rounds of selection using a non-immune yeast display library that contained as many as 109 single chain variable fragments (scFv). Two unique clones with low KD values (RA4 and RA8) were then selected to construct fully human anti-CD25 antibodies (IgG1/kappa) for stable expression. One antibody, RA8, showed excellent binding to human CD25+ cell lines and to human Treg cells and appears to be an excellent candidate for the generation of a human reagent that may be used in man for the immunotherapy of cancer.

  2. Anti-CD25 monoclonal antibody Fc variants differentially impact regulatory T cells and immune homeostasis.

    Science.gov (United States)

    Huss, David J; Pellerin, Alex F; Collette, Brian P; Kannan, Arun K; Peng, Liaomin; Datta, Abhishek; Wipke, Brian T; Fontenot, Jason D

    2016-07-01

    Interleukin-2 (IL-2) is a critical regulator of immune homeostasis through its non-redundant role in regulatory T (Treg) cell biology. There is major interest in therapeutic modulation of the IL-2 pathway to promote immune activation in the context of tumour immunotherapy or to enhance immune suppression in the context of transplantation, autoimmunity and inflammatory diseases. Antibody-mediated targeting of the high-affinity IL-2 receptor α chain (IL-2Rα or CD25) offers a direct mechanism to target IL-2 biology and is being actively explored in the clinic. In mouse models, the rat anti-mouse CD25 clone PC61 has been used extensively to investigate the biology of IL-2 and Treg cells; however, there has been controversy and conflicting data on the exact in vivo mechanistic function of PC61. Engineering antibodies to alter Fc/Fc receptor interactions can significantly alter their in vivo function. In this study, we re-engineered the heavy chain constant region of an anti-CD25 monoclonal antibody to generate variants with highly divergent Fc effector function. Using these anti-CD25 Fc variants in multiple mouse models, we investigated the in vivo impact of CD25 blockade versus depletion of CD25(+) Treg cells on immune homeostasis. We report that immune homeostasis can be maintained during CD25 blockade but aberrant T-cell activation prevails when CD25(+) Treg cells are actively depleted. These results clarify the impact of PC61 on Treg cell biology and reveal an important distinction between CD25 blockade and depletion of CD25(+) Treg cells. These findings should inform therapeutic manipulation of the IL-2 pathway by targeting the high-affinity IL-2R. PMID:27012310

  3. Incomplete depletion and rapid regeneration of Foxp3+ regulatory T cells following anti-CD25 treatment in malaria-infected mice

    OpenAIRE

    Couper, Kevin N.; Blount, Daniel G.; de Souza, J. Brian; Suffia, Isabelle; Belkaid, Yasmine; Riley, Eleanor M.

    2007-01-01

    Investigation of the role of regulatory T cells (Treg) in model systems is facilitated by their depletion using anti-CD25 antibodies, but there has been considerable debate about the effectiveness of this strategy. Here, we have compared the depletion and repopulation of CD4+CD25+Foxp3+ Treg in uninfected and malaria-infected mice using 7D4 and/or PC61 anti-CD25 antibodies. We find that numbers and percentages of CD25hi cells, but not Foxp3+ cells, are transiently reduced after 7D4 treatment ...

  4. Immunotherapy

    Science.gov (United States)

    ... Help raise $300,000 this month to find cures. Loading... Immunotherapy Immunotherapy SHARE: Print Glossary Immunotherapy, also ... destroy the antigens. In most circumstances, the body's natural immune system seems unable to identify cancer as ...

  5. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

    Science.gov (United States)

    Janik, John E.; Morris, John C.; O’Mahony, Deirdre; Pittaluga, Stefania; Jaffe, Elaine S.; Redon, Christophe E.; Bonner, William M.; Brechbiel, Martin W.; Paik, Chang H.; Whatley, Millie; Chen, Clara; Lee, Jae-Ho; Fleisher, Thomas A.; Brown, Maggie; White, Jeffrey D.; Stewart, Donn M.; Fioravanti, Suzanne; Lee, Cathryn C.; Goldman, Carolyn K.; Bryant, Bonita R.; Junghans, Richard P.; Carrasquillo, Jorge A.; Worthy, Tat’Yana; Corcoran, Erin; Conlon, Kevin C.; Waldmann, Thomas A.

    2015-01-01

    Despite significant advances in the treatment of Hodgkin’s lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed–Sternberg cells and by most polyclonal T cells rosetting around Reed–Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody 90Y-daclizumab. 90Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with 90Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed–Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25− provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated 90Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed–Sternberg cells provided meaningful therapy for select HL patients. PMID:26438866

  6. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma.

    Science.gov (United States)

    Janik, John E; Morris, John C; O'Mahony, Deirdre; Pittaluga, Stefania; Jaffe, Elaine S; Redon, Christophe E; Bonner, William M; Brechbiel, Martin W; Paik, Chang H; Whatley, Millie; Chen, Clara; Lee, Jae-Ho; Fleisher, Thomas A; Brown, Maggie; White, Jeffrey D; Stewart, Donn M; Fioravanti, Suzanne; Lee, Cathryn C; Goldman, Carolyn K; Bryant, Bonita R; Junghans, Richard P; Carrasquillo, Jorge A; Worthy, Tat'Yana; Corcoran, Erin; Conlon, Kevin C; Waldmann, Thomas A

    2015-10-20

    Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody (90)Y-daclizumab. (90)Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with (90)Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25(-) provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated (90)Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients. PMID:26438866

  7. Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Zong Sheng eGuo

    2014-04-01

    Full Text Available Oncolytic viruses (OVs are novel immunotherapeutic agents whose anticancer effects come from both oncolysis and elicited antitumor immunity. OVs induce mostly immunogenic cancer cell death (ICD, including immunogenic apoptosis, necrosis/necroptosis, pyroptosis and autophagic cell death, leading to exposure of calreticulin and heat-shock proteins to the cell surface, and/or released ATP, high mobility group box-1 [HMGB1], uric acid, and other DAMPs as well as PAMPs as danger signals, along with tumor-associated antigens, to activate dendritic cells (DCs and elicit adaptive antitumor immunity. Dying the right way may greatly potentiate adaptive antitumor immunity. The mode of cancer cell death may be modulated by individual OVs and cancer cells as they often encode and express genes that inhibit/promote apoptosis, necroptosis or autophagic cell death. We can genetically engineer OVs with death-pathway-modulating genes and thus skew the infected cancer cells towards certain death pathways for the enhanced immunogenicity. Strategies combining with some standard therapeutic regimens may also change the immunological consequence of cancer cell death. In this review, we discuss recent advances in our understanding of danger signals, modes of cancer cell death induced by OVs, the induced danger signals and functions in eliciting subsequent antitumor immunity. We also discuss potential combination strategies to target cells into specific modes of ICD and enhance cancer immunogenicity, including blockade of immune checkpoints, in order to break immune tolerance, improve antitumor immunity and thus the overall therapeutic efficacy.

  8. Administration of anti-CD25 mAb leads to impaired alpha-galactosylceramide-mediated induction of IFN-gamma production in a murine model

    Czech Academy of Sciences Publication Activity Database

    Rosalia, Rodney Alexander; Štěpánek, Ivan; Polláková, Veronika; Šímová, Jana; Bieblová, Jana; Indrová, Marie; Moravcová, Simona; Přibylová, Hana; Bontkes, H.; Bubeník, Jan; Sparwasser, T.; Reiniš, Milan

    2013-01-01

    Roč. 218, č. 6 (2013), s. 851-859. ISSN 0171-2985 R&D Projects: GA ČR GA301/07/1410; GA ČR GAP301/10/2174 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : cancer immunotherapy * DEREG mice * interferon γ * natural killer T cells * PC61 monoclonal antibody * T regulatory cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.180, year: 2013

  9. Sarcoma Immunotherapy

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    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.

  10. Sarcoma Immunotherapy

    International Nuclear Information System (INIS)

    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

  11. Classification of current anticancer immunotherapies

    Science.gov (United States)

    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  12. Heat shock proteins and immunotherapy

    Institute of Scientific and Technical Information of China (English)

    XinZHAO; XueMeiXU; GuoxingSONG

    2005-01-01

    Being one of the most abundant intracellular proteins,heat shock proteins(HSPs) have many housekeeping functions which are crucial for the survival of organisms.In addition,some HSPs are new immunoactive molecules which play important roles in both adaptive and innate immunity.They could activate CD8+ and CD4+ lymphocytes,induce innate immune response including natural killer(NK) cell activation and cytokine secretion,and induce maturation of dendritic cells(DCs).These characteristics have been used for immunotherapy of various types of cancers and infectious disenses.This review focuses on the main HSP families——HSP70 and 90 families.The mechanism of HSPs’ function in eliciting immune response are elucidated and various forms of HSPs used in immunotherapy are discussed in details.At the end of this review,authors summarize clinical trials related to HSPs and evaluate their clinical efficacy.

  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. Trends in Cancer Immunotherapy

    OpenAIRE

    Murphy, Joseph F.

    2010-01-01

    Modulation of the immune system for therapeutic ends has a long history, stretching back to Edward Jenner’s use of cowpox to induce immunity to smallpox in 1796. Since then, immunotherapy, in the form of prophylactic and therapeutic vaccines, has enabled doctors to treat and prevent a variety of infectious diseases, including cholera, poliomyelitis, diphtheria, measles and mumps. Immunotherapy is now increasingly being applied to oncology. Cancer immunotherapy attempts to harness the power an...

  15. 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.

  16. Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

    Science.gov (United States)

    Whelan, M C; Casey, G; MacConmara, M; Lederer, J A; Soden, D; Collins, J K; Tangney, M; O'Sullivan, G C

    2010-07-01

    Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development. PMID:20186173

  17. Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

    LENUS (Irish Health Repository)

    Whelan, M C

    2012-01-31

    Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development.

  18. 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.

  19. 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

  20. 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.

  1. BRAIN CANCER IMMUNOTHERAPY (REVIEW)

    OpenAIRE

    Yashin К.S.; Medyanik I.А.

    2014-01-01

    The review analyzes Russian and foreign reports concerned with a rapidly developing brain cancer treatment technique — immunotherapy. There has been presented a current view on the basic concept of antitumor immunity, on the problem of immune system interaction with a tumor in general and under the conditions of an immunologically privileged nervous system, shown the theoretical background of efficiency of immunotherapy used against brain cancer (the capability of tumor antigens and activated...

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

    International Nuclear Information System (INIS)

    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

  3. Cancer immunotherapy with surgery

    Directory of Open Access Journals (Sweden)

    Orita,Kunzo

    1977-08-01

    Full Text Available With the recent advances in the immunological surveillance system, an understanding of the role of host immunity has become essential to the management of carcinogenesis, tumor proliferation, recurrence and metastasis. Although it is important to continue chemical and surgical treatment of cancer, support of the anti-tumor immune system of the host should also be considered. Long term remission has been reported in leukemia by treating with BCG after chemotherapy whereas surgical treatment is usually more effective in preventing cancer recurrence in digestive organ cancer. The first step is extirpating the tumor as thoroughly as possible and the second step is chemo-immunotherapy. Cancer immunity, however weak, constitutes the basis for other treatments in selectively attacking cancer cells remaining after surgery, chemotherapy or irradiation. Immunotherapy should thus not replace chemotherapy or radiotherapy, but these methods should be employed in combination to attain more favorable results.

  4. 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 in......-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...

  5. Immunotherapy of Melanoma.

    Science.gov (United States)

    Snyder, Alexandra; Zamarin, Dmitriy; Wolchok, Jedd D

    2015-01-01

    The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1. Therapies intended to 'reeducate' T cells, such as tumor-infiltrating lymphocyte therapy, oncolytic viruses and tumor vaccines, have yielded promising results and are under development. Finally, the integration of the above therapies as well as development of new coinhibitory and costimulatory agents, though in early stages, appear very promising and likely represent the next phase in drug development for the treatment of metastatic melanoma. PMID:26376963

  6. Bladder cancer immunotherapy.

    Science.gov (United States)

    Lamm, D L; Thor, D E; Stogdill, V D; Radwin, H M

    1982-11-01

    A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder. In addition, 9 patients at high risk for tumor recurrence were treated with bacillus Calmette-Guerin produced a self-limited cystitis and 1 complication (hydronephrosis) of immunotherapy was observed. Of the 57 randomized patients 54 were followed for 3 to 30 months. Tumor recurrence was documented in 13 of 26 controls (50 per cent) and only 6 of 28 patients (21 per cent) treated with bacillus Calmette-Guerin (p equals 0.027, chi-square). The interval free of disease was prolonged significantly with bacillus Calmette-Guerin treatment (p equals 0.014, generalized Wilcoxon test). Importantly, a simple purified protein derivative skin test distinguished those patients who responded to bacillus Calmette-Guerin immunotherapy from those who did not. Only 1 of 17 treated patients (6 per cent) whose purified protein derivative test converted from negative to positive had tumor recurrence compared to 5 recurrences (38 per cent) among the 13 patients whose test remained negative or had been positive before treatment (p equals 0.022, chi-square). Bacillus Calmette-Guerin was given to 10 patients with stage B transitional cell carcinoma who were not candidates for cystectomy and 7 are free of disease. Of 5 patients with carcinoma in situ 3 remain free of tumor after bacillus Calmette-Guerin treatment and 5 of 6 who had multiple recurrences after intravesical chemotherapy responded favorably to bacillus Calmette-Guerin immunotherapy. PMID:6757467

  7. 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.

  8. Brain Cancer Immunotherapy (Review

    Directory of Open Access Journals (Sweden)

    Yashin К.S.

    2014-12-01

    Full Text Available The review analyzes Russian and foreign reports concerned with a rapidly developing brain cancer treatment technique — immunotherapy. There has been presented a current view on the basic concept of antitumor immunity, on the problem of immune system interaction with a tumor in general and under the conditions of an immunologically privileged nervous system, shown the theoretical background of efficiency of immunotherapy used against brain cancer (the capability of tumor antigens and activated lymphocytes to penetrate the blood-brain barrier. There has been demonstrated the role of a transforming growth factor β, interleukin 10, cyclooxygenase-2, prostaglandin Е2, protein MCP-1, interactions Fas-receptor/Fas-ligand, antigen-4 cytotoxic Т-lymphocytes in tumor immunoresistance development. The review presents a current classification of the types of active and passive immunotherapy, each of the types being considered separately specifying the characteristics, the results of preclinical and clinical trials of each type efficiency, and possible side effects. Special attention has been paid to a new concept of a key role of tumor stem cells in the pathogenesis of cerebral gliomas and the target action on these cells.

  9. Immunotherapy and immunoescape in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    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 IFNy 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.

  10. [Immunotherapy for Alzheimer's disease].

    Science.gov (United States)

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers

    2016-01-18

    Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD. Solanezumab and new monoclonal antibodies are being tested in patients with prodromal and preclinical AD in search for a disease-modifying treatment. PMID:26815584

  11. CCL21 Cancer Immunotherapy

    International Nuclear Information System (INIS)

    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

  12. Cellular immunotherapy directed against human cytomegalovirus as a novel approach for glioblastoma treatment

    OpenAIRE

    Schuessler, Andrea; Walker, David G.; Khanna, Rajiv

    2014-01-01

    Glioblastoma multiforme (GBM) has a very poor prognosis, despite multimodal therapy including surgery, radiation and chemotherapy. A novel adoptive immunotherapy that exploits the presence of cytomegalovirus antigens in malignant brain cancer cells has been shown to be safe and elicit potential clinical benefit for the treatment of recurrent GBM.

  13. Ludic Elicitation: Using Games for Knowledge Elicitation

    Science.gov (United States)

    Cao, Yan

    2014-01-01

    Knowledge elicitation from human beings is important for many fields, such as decision support systems, risk communication, and customer preference studying. Traditional approaches include observations, questionnaires, structured and semi-structured interviews, and group discussions. Many publications have been studying different techniques for a…

  14. 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. PMID:22264261

  15. Adherence to Sublingual Immunotherapy.

    Science.gov (United States)

    Incorvaia, Cristoforo; Mauro, Marina; Leo, Gualtiero; Ridolo, Erminia

    2016-02-01

    Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13% of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment. PMID:26758865

  16. Inmunoterapia local Local immunotherapy

    Directory of Open Access Journals (Sweden)

    E. Lasa

    2003-01-01

    Full Text Available La inmunoterapia específica, junto con la evitación del alergeno y el tratamiento sintomático, forma parte del tratamiento de la patología alérgica. La modalidad más antigua, más conocida y mejor estudiada es la inmunoterapia subcutánea (ITSC, cuya eficacia tanto a corto como a largo plazo, ha sido ampliamente demostrada en numerosos estudios. Sin embargo, a pesar de haberse demostrado segura, no está exenta de efectos adversos y precisa ser administrada bajo supervisión de personal médico. Esto ha animado a buscar nuevas vías de administración de eficacia similar, con un buen perfil de seguridad, y de buena cumplimentación por parte del paciente. De las distintas alternativas estudiadas la más relevante es la inmunoterapia sublingual (ITSL. En ésta, se administra el antígeno en forma de gotas debajo de la lengua. Existen diferentes pautas de administración en función del alergeno implicado. La dosis óptima de tratamiento está aún sin determinar, hallándose en este momento en un rango amplio de dosis respecto a la inmunoterapia subcutánea. Su mecanismo de acción es poco conocido aunque en diversos estudios se han observado cambios inmunológicos. La ITSL ha mostrado un buen perfil de seguridad con escasos efectos secundarios, habitualmente de carácter local. Asimismo se han realizado distintos ensayos clínicos en los que se ha demostrado su eficacia en el tratamiento de la alergia respiratoria tanto en niños como en adultos. Por ello, aunque aún existen datos sin resolver respecto a esta vía de administración de inmunoterapia, ha sido propuesta por la OMS como una alternativa válida a la ITSC.Specific immunotherapy, together with avoidance of the allergen and symptomatic treatment, forms part of the treatment of allergic pathology. The oldest, best known and most studied form is subcutaneous immunotherapy (SCIT, whose efficacy, both in the short and the long term, has been widely demonstrated in numerous studies

  17. Mouse Models of Tumor Immunotherapy.

    Science.gov (United States)

    Ngiow, Shin Foong; Loi, Sherene; Thomas, David; Smyth, Mark J

    2016-01-01

    Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy agents will be developed and assessed for their therapeutic activity. In light of this, in vivo experimental mouse models that recapitulate human malignancies serve as valuable tools to validate the efficacy and safety profile of immunotherapy agents, before their transition into clinical trials. In this review, we will discuss the major classes of experimental mouse models of cancer commonly used for immunotherapy assessment and provide examples to guide the selection of appropriate models. We present some new data concerning the utility of a carcinogen-induced tumor model for comparing immunotherapies and combining immunotherapy with chemotherapy. We will also highlight some recent advances in experimental modeling of human malignancies in mice that are leading towards personalized therapy in patients. PMID:26922998

  18. Modified immunotherapy for alopecia areata.

    Science.gov (United States)

    Yoshimasu, Takashi; Furukawa, Fukumi

    2016-07-01

    Squaric acid dibutylester (SADBE) is a commonly used contact sensitizer in immunotherapy for alopecia areata (AA). Severe contact dermatitis is induced by the currently high recommended sensitization dose of 1%-2% SADBE, often decreasing patient compliance. We assessed a modified immunotherapy for AA using SADBE at a starting concentration of 0.01% without sensitization. After one or two weeks of initial 0.01% SADBE application, the concentration of SADBE was increased gradually to 0.025%, 0.05%, 0.1%, 0.25%, 0.5%, 1% and 2% until the patients felt itching or erythema at the AA lesion site. The modified immunotherapy showed a response rate of 69.4% (25/36), equivalent to conventional immunotherapy using SADBE starting at 1%-2% sensitization. Furthermore, we investigated the combination therapy of SADBE and multiple courses of steroid pulses for AA. The response rate for combination therapy was 73.7% (28/38); however, the group receiving combination therapy showed a significant prevalence of severe AA compared with the group receiving modified immunotherapy only. We reviewed the efficacy and safety of modified immunotherapy without initial sensitization and combination therapy with immunotherapy and multiple courses of pulses for AA. PMID:26932732

  19. 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. PMID:24088073

  20. Immunotherapy for bladder cancer

    Directory of Open Access Journals (Sweden)

    Fuge O

    2015-05-01

    Full Text Available Oliver Fuge,1 Nikhil Vasdev,1 Paula Allchorne,2 James SA Green2 1Department of Urology, Lister Hospital, Stevenage, UK; 2Department of Urology, Bartshealth NHS Trust, Whipps Cross Rd, London, UK Abstract: It is nearly 40 years since Bacillus Calmette–Guérin (BCG was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest

  1. Imaging Biomarkers in Immunotherapy

    Science.gov (United States)

    Juergens, Rosalyn A.; Zukotynski, Katherine A.; Singnurkar, Amit; Snider, Denis P.; Valliant, John F.; Gulenchyn, Karen Y.

    2016-01-01

    Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer. PMID:26949344

  2. Immunotherapy for bladder cancer.

    Science.gov (United States)

    Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James Sa

    2015-01-01

    It is nearly 40 years since Bacillus Calmette-Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

  3. Belief Elicitation in Experiments

    DEFF Research Database (Denmark)

    Blanco, Mariana; Engelmann, Dirk; Koch, Alexander;

    in the experiment. This raises two questions: (i) can we trust the existing belief elicitation results, (ii) can we avoid potential hedging confounds? Our results instill confidence regarding both issues. We propose an experimental design that eliminates hedging opportunities, and use this to test...... for the empirical relevance of hedging effects in the lab. We find no evidence for hedging, comparing the standard 'hedging-prone' belief elicitation treatment to a 'hedging-proof' design in a sequential prisoners' dilemma game. Our findings are strengthened by the absence of hedging even in an...... additional non-belief elicitation treatment using a financial investment frame, where hedging arguably would be most natural....

  4. 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....

  5. Cancer Immunotherapy of Targeting Angiogenesis

    Institute of Scientific and Technical Information of China (English)

    JianmeiHou; LingTian; YuquanWei

    2004-01-01

    Tumor growth and metastasis are angiogenesis-dependent. Anti-angiogenic therapy may be a useful approach to cancer therapy. This review discussed tumor angiogenesis and immunotherapy of targeting tumor angiogenesis from two main aspects: (1) active vaccination to induce effective anti-angiogenesis immunity; (2) passive immunotherapy with anti-pro-angiogenic molecules relevant antibody. Evidence from the recent years suggested that anti-angiogenic therapy should be one of the most promising approaches to cancer therapy.

  6. Cancer Immunotherapy: A Review

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2016-04-01

    Full Text Available BACKGROUND: The goals of treating patients with cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. Therefore, stimulating immune reactions to tumors can be an attractive therapeutic and prevention strategy. CONTENT: During immune surveillance, the host provides defense against foreign antigens, while ensuring it limits activation against self antigens. By targeting surface antigens expressed on tumor cells, monoclonal antibodies have demonstrated efficacy as cancer therapeutics. Recent successful antibody-based strategies have focused on enhancing antitumor immune responses by targeting immune cells, irrespective of tumor antigens. The use of antibodies to block pathways inhibiting the endogenous immune response to cancer, known as checkpoint blockade therapy, has stirred up a great deal of excitement among scientists, physicians, and patients alike. Clinical trials evaluating the safety and efficacy of antibodies that block the T cell inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4 and programmed cell death 1 (PD-1 have reported success in treating subsets of patients. Adoptive cell transfer (ACT is a highly personalized cancer therapy that involve administration to the cancer-bearing host of immune cells with direct anticancer activity. In addition, the ability to genetically engineer lymphocytes to express conventional T cell receptors or chimeric antigen receptors has further extended the successful application of ACT for cancer treatment. SUMMARY: For cancer treatment, 2011 marked the beginning of a new era. The underlying basis of cancer immunotherapy is to activate a patient’s own T cells so that they can kill their tumors. Reports of amazing recoveries abound, where patients remain cancer-free many years after receiving the therapy. The idea of harnessing immune cells to fight cancer is

  7. Immunotherapy for malignant glioma

    Directory of Open Access Journals (Sweden)

    Carter M Suryadevara

    2015-01-01

    Full Text Available Malignant gliomas (MG are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM, the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.

  8. Development of cancer immunotherapy

    International Nuclear Information System (INIS)

    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

  9. Immunotherapy of Brain Cancer.

    Science.gov (United States)

    Roth, Patrick; Preusser, Matthias; Weller, Michael

    2016-01-01

    The brain has long been considered an immune-privileged site precluding potent immune responses. Nevertheless, because of the failure of conventional anti-cancer treatments to achieve sustained control of intracranial neoplasms, immunotherapy has been considered as a promising strategy for decades. However, several efforts aimed at exploiting the immune system as a therapeutic weapon were largely unsuccessful. The situation only changed with the introduction of the checkpoint inhibitors, which target immune cell receptors that interfere with the activation of immune effector cells. Following the observation of striking effects of drugs that target CTLA-4 or PD-1 against melanoma and other tumor entities, it was recognized that these drugs may also be active against metastatic tumor lesions in the brain. Their therapeutic activity against primary brain tumors is currently being investigated within clinical trials. In parallel, other immunotherapeutics such as peptide vaccines are at an advanced stage of clinical development. Further immunotherapeutic strategies currently under investigation comprise adoptive immune cell transfer as well as inhibitors of metabolic pathways involved in the local immunosuppression frequently found in brain tumors. Thus, the ongoing implementation of immunotherapeutic concepts into clinical routine may represent a powerful addition to the therapeutic arsenal against various brain tumors. PMID:27260656

  10. 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.

  11. Anti-amyloid-beta to tau-based immunization: developments in immunotherapy for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lambracht-Washington D

    2013-08-01

    Full Text Available Doris Lambracht-Washington, Roger N Rosenberg Department of Neurology and Neurotherapeutics, Alzheimer's Disease Center, University of Texas Southwestern Medical Center, Dallas, TX, USA Abstract: Immunotherapy might provide an effective treatment for Alzheimer's disease (AD. A unique feature of AD immunotherapies is that an immune response against a self-antigen needs to be elicited without causing adverse autoimmune reactions. Current research is focused on two possible targets in this regard. One is the inhibition of accumulation and deposition of amyloid beta 1–42 (Aβ42, which is one of the major peptides found in senile plaques, and the second target is hyperphosphorylated tau, which forms neurofibrillary tangles inside the nerve cell and shows association with the progression of dementia. Mouse models have shown that immunotherapy targeting Aβ42 as well as tau with the respective anti-Aβ or anti-tau antibodies can provide significant improvements in these mice. While anti-Aβ immunotherapy (active and passive immunizations is already in several stages of clinical trials, tau-based immunizations have been analyzed only in mouse models. Recently, as a significant correlation of progression of dementia and levels of phosphorylated tau have been found, high interest has again focused on further development of tau-based therapies. While Aβ immunotherapy might delay the onset of AD, immunotherapy targeting tau might provide benefits in later stages of this disease. Last but not least, targeting Aβ and tau simultaneously with immunotherapy might provide additional therapeutic effects, as these two pathologies are likely synergistic; this is an approach that has not been tested yet. In this review, we will summarize animal models used to test possible therapies for AD, some of the facts about Aβ42 and tau biology, and present an overview on halted, ongoing, and upcoming clinical trials together with ongoing preclinical studies targeting tau

  12. Acquired resistance to immunotherapy and future challenges.

    Science.gov (United States)

    Restifo, Nicholas P; Smyth, Mark J; Snyder, Alexandra

    2016-02-01

    Advances in immunotherapy have resulted in remarkable clinical responses in some patients. However, one of the biggest challenges in cancer therapeutics is the development of resistant disease and disease progression on or after therapy. Given that many patients have now received various types of immunotherapy, we asked three scientists to give their views on the current evidence for whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy. PMID:26822578

  13. Adoptive immunotherapy via CD4+ versus CD8+ T cells

    Directory of Open Access Journals (Sweden)

    Vy Phan-Lai

    2016-04-01

    Full Text Available The goal of cancer immunotherapy is to induce specific and durable antitumor immunity. Adoptive T cell therapy (ACT has garnered wide interest, particularly in regard to strategies to improve T cell efficacy in trials. There are many types of T cells (and subsets which can be selected for use in ACT. CD4+ T cells are critical for the regulation, activation and aid of host defense mechanisms and, importantly, for enhancing the function of tumor-specific CD8+ T cells. To date, much research in cancer immunotherapy has focused on CD8+ T cells, in melanoma and other cancers. Both CD4+ T cells and CD8+ T cells have been evaluated as ACT in mice and humans, and both are effective at eliciting antitumor responses. IL-17 producing CD4+ T cells are a new subset of CD4+ T cells to be evaluated in ACT models. This review discusses the benefits of adoptive immunotherapy mediated by CD8+ and CD4+ cells. It also discusses the various type of T cells, source of T cells, and ex vivo cytokine growth factors for augmenting clinical efficacy of ACT. [Biomed Res Ther 2016; 3(4.000: 588-595

  14. 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.

  15. Immunotherapy of Childhood Sarcomas.

    Science.gov (United States)

    Roberts, Stephen S; Chou, Alexander J; Cheung, Nai-Kong V

    2015-01-01

    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 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 CTLA-4 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. PMID:26301204

  16. 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. PMID:26558320

  17. Immunotherapy for tuberculosis: future prospects

    Directory of Open Access Journals (Sweden)

    Abate G

    2016-04-01

    Full Text Available Getahun Abate,1 Daniel F Hoft1,2 1Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, 2Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO, USA Abstract: Tuberculosis (TB is still a major global health problem. A third of the world's population is infected with Mycobacterium tuberculosis. Only ~10% of infected individuals develop TB but there are 9 million TB cases with 1.5 million deaths annually. The standard prophylactic treatment regimens for latent TB infection take 3–9 months, and new cases of TB require at least 6 months of treatment with multiple drugs. The management of latent TB infection and TB has become more challenging because of the spread of multidrug-resistant and extremely drug-resistant TB. Intensified efforts to find new TB drugs and immunotherapies are needed. Immunotherapies could modulate the immune system in patients with latent TB infection or active disease, enabling better control of M. tuberculosis replication. This review describes several types of potential immunotherapies with a focus on those which have been tested in humans. Keywords: tuberculosis, HDT, immunotherapy, treatment

  18. 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 AI...

  19. The immunotherapy of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Weksler Marc E

    2004-11-01

    Full Text Available Abstract Only a small percentage of patients with Alzheimer's disease benefit from current drug therapy and for only a relatively short time. This is not surprising as the goal of these drugs is to enhance existing cerebral function in Alzheimer patients and not to block the progression of cognitive decline. In contrast, immunotherapy is directed at clearing the neurotoxic amyloid beta peptide from the brain that directly or indirectly leads to cognitive decline in patients with Alzheimer's disease. The single trial of active immunization with the amyloid beta peptide provided suggestive evidence of a reduction in cerebral amyloid plaques and of stabilization in cognitive function of half the patients who developed good antibody responses to the amyloid beta peptide. However, 6% of actively immunized Alzheimer patients developed sterile meningoencephalitis that forced the cessation of the clinical trial. Passive immunotherapy in animal models of Alzheimer's disease has provided similar benefits comparable to those seen with active immunotherapy and has the potential of being effective in the half of Alzheimer's disease patients who do not make a significant anti-amyloid beta peptide antibody response and without inducing T-cell-mediated encephalitis. Published studies of 5 patients with sporadic Alzheimer disease treated with intravenous immunoglobulin containing anti-amyloid beta peptide antibodies showed that amyloid beta peptide was mobilized from the brain and cognitive decline was interrupted. Further studies of passive immunotherapy are urgently required to confirm these observations.

  20. Cancer-testis antigens and immunotherapy in the light of cancer complexity.

    Science.gov (United States)

    Grizzi, F; Mirandola, L; Qehajaj, D; Cobos, E; Figueroa, J A; Chiriva-Internati, M

    2015-03-01

    The ability of immunotherapy to evoke successful antitumor immune responses has been well documented over the past decade. Despite abundant preclinical data, it is only with the recent approval by the Food and Drug Administration (FDA) of the drugs such as sipuleucel-T and ipilimumab that immunotherapy is finally being recognized as a viable alternative to traditional therapies for treatment of various cancers. Despite the ability of immunotherapy to elicit successful antitumor immune responses, its efficacy is hindered by several factors. Among these are the paucity of tumor-associated antigens (TAA) that can be used as effective targets and the systemic toxicities that often lead to treatment interruption. Indeed, such adverse effects, which can be immunological and/or parenchymal, can be particularly severe and even fatal to some patients. A family of TAA called cancer-testis antigens (CTA) has been identified and their encoding genes have been extensively investigated. CTA expression has been demonstrated in a variety of human cancer tissues, and at least 19 CTA have been found to elicit humoral and/or cellular immune responses in cancer patients. Here we discuss how CTA and immunotherapy will most likely play a major role in the cure of cancer in the light of cancer complexity. PMID:25901859

  1. Automated Preferences Elicitation

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav; Guy, Tatiana Valentine

    Prague : Institute of Information Theory and Automation, 2011, s. 20-25. ISBN 978-80-903834-6-3. [The 2nd International Workshop od Decision Making with Multiple Imperfect Decision Makers. Held in Conjunction with the 25th Annual Conference on Neural Information Processing Systems (NIPS 2011). Sierra Nevada (ES), 16.12.2011-16.12.2011] R&D Projects: GA MŠk 1M0572; GA ČR GA102/08/0567 Institutional research plan: CEZ:AV0Z10750506 Keywords : elicitation * decision making * Bayesian decision making * fully probabilistic design Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2011/AS/karny-automated preferences elicitation.pdf

  2. Recent progress in allergen immunotherapy.

    Science.gov (United States)

    Nouri-Aria, Kayhan T

    2008-03-01

    The efficacy of allergen immunotherapy for the treatment of allergic rhinoconjunctivitis with or without seasonal bronchial asthma and anaphylaxis caused by the sting of the hymenoptera class of insects has been clearly demonstrated in numerous well-designed, placebo-controlled trials. Immunotherapy whether by subcutaneous injection of allergen extract or by oral/sublingual routes modifies peripheral and mucosal TH2 responses in favour of TH1 responses and augments IL-10 synthesis by TRegs both locally and by peripheral T cells. Recent researches into the cellular and molecular basis of allergic reactions have advanced our understanding of the mechanisms involved in allergic diseases. They have also helped the development of innovative approaches that are likely to further improve the control of allergic responses in the future. Novel approaches to immunotherapy that are currently being explored include the use of peptide-based allergen preparations, which do not bind IgE and therefore do not activate mast cells, but reduce both Th1 and Th2-cytokine synthesis, while increasing levels of IL-10. Alternative strategies include the use of adjuvants, such as nucleotide immunostimulatory sequences derived from bacteria CpG or monophosphoryl lipid A that potentiate Th1 responses. Blocking the effects of IgE using anti-IgE such as omalizumab, a recombinant humanized monoclonal antibody that selectively binds to IgE, has been shown to be a useful strategy in the treatment of allergic asthma and rhinitis. The combination of anti-IgE-monoclonal antibody omalizumab with allergen immunotherapy has proved beneficial for the treatment of allergic diseases, offering improved efficacy, limited adverse effects, and potential immune-modifying effects. This combination may also accelerate the rapidity by which immunotherapy induces TReg cells. If allergic diseases are due to a lack of allergen-specific TReg cells, then effective therapies should target the induction and the

  3. New Concepts in Tumor Antigens: Their Significance in Future Immunotherapies for Tumors

    Institute of Scientific and Technical Information of China (English)

    Fan Yang; Xiao-Feng Yang

    2005-01-01

    The identification and molecular characterization of self-antigens expressed by human malignancies that are capable of elicitation of anti-tumor immune responses in patients have been an active field in tumor immunology.More than 2,000 tumor antigens have been identified, and most of these antigens are self-antigens. These significant progresses have led to the renaissance of tumor immunology and studies on anti-tumor immunotherapy.However, despite of the progress in the identification of self-tumor antigens, current antigen-specific immunotherapies for tumors are far less satisfied than expected, which reflects the urgent need to improve our understanding on self-tumor antigens. In order to develop more effective antigen specific anti-tumor immunotherapies and to monitor the responses to these immunotherapies in patients with tumors, many important fundamental questions need to be addressed. We propose for the first time that the studies in addressing the characteristics of self-tumor antigens and autoantigens are grouped as a new subject termed "antigenology". In this brief review, we would outline the progress in the identification of tumor antigens in solid tumors and hematologic malignancies, and overview the new concepts and principles of antigenology and their significance for future immunotherapies to these malignancies. Cellular & Molecular Immunology.

  4. Experimental studies of tumor immunotherapy. II. Tumor immunotherapy following tumor extirpation

    Directory of Open Access Journals (Sweden)

    Hayashi,Shigeo

    1976-06-01

    Full Text Available In order to approach human cancer immunotherapy, the author carried out the immunotherapy with BCG on mice having homotransplanted cancer, observed the posttransplantation results with lapse of time, conduced daily macrophage inhibition test (MI test and found the immunotherapy to be effective. At the same time the MI test proved to be a useful criterion in determining the course of cancer progress and effectiveness of the immunotherapy.

  5. Allergen immunotherapy in polysensitized patient.

    Science.gov (United States)

    Hrubiško, M; Špičák, V

    2016-05-01

    Specific allergen immunotherapy (AIT) is the only therapeutic method with positive impact on natural course of allergic disease - affecting clinical development (including the progression of rhinitis to asthma) and new sensitisations. The actual problem is the increasing number of patients manifesting poly-sensitivity in allergy skin tests and / or in specific IgE tests. Usually, AIT is not recommended in such individuals. The objective we are facing is that in many patients tested as poly-reactive, we have to distinguish in which cases it is a true polysensitization, and when it is due to cross-reactivity of specific IgE antibodies induced by panallergens. This may really determine when AIT may be an appropriate course of action. The article focuses on this problem in more detail, applying the long time Czech and Slovak experience with allergy testing and allergen immunotherapy. PMID:27152601

  6. Emerging immunotherapy in pediatric lymphoma.

    Science.gov (United States)

    Erker, Craig; Harker-Murray, Paul; Burke, Michael J

    2016-01-01

    Hodgkin and non-Hodgkin lymphoma collectively are the third most common cancer diagnosed in children each year. For children who relapse or have refractory disease, outcomes remain poor. Immunotherapy has recently emerged as a novel approach to treat hematologic malignancies. The field has been rapidly expanding over the past few years broadening its armamentarium which now includes monoclonal antibodies, antibody-drug conjugates and cellular therapies including bispecific T-cell engagers and chimeric antigen receptor-engineered T cells. Many of these agents are in their infancy stages and only beginning to make their mark on lymphoma treatment while others have begun to show promising efficacy in relapsed disease. In this review, the authors provide an overview of current and emerging immunotherapies in the field of pediatric lymphoma. PMID:26616565

  7. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2012-01-01

    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......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...

  8. New strategies for allergen immunotherapy.

    Science.gov (United States)

    Carnés, Jerónimo; Robinson, Douglas S

    2008-06-01

    Specific allergen immunotherapy, consisting in the administration of increasing amounts of offending allergens into sensitive patients was first used nearly one hundred years ago and remains in use worldwide for treatment of allergic rhinitis and asthma. It has been recognised as the only effective treatment for type I allergic diseases when the appropriate quantities of allergens are used. The immunological mechanisms by which specific immunotherapy is effective include the modulation of T cells and the response of B-cells and is accompanied by significant decreases of specific IgE and increases in allergen specific IgG antibodies, mainly IgG4. While specific allergen injection immunotherapy is highly effective and the most common way of administration other routes such as oral or intranasal ways have been considered as and alternative to subcutaneous injections. During the last century, allergenic vaccines have been prepared using individual allergens adsorbed to different adjuvant substances. These vaccines have demonstrated efficacy and good results in different clinical trials. However, many novel approaches to allergen immunotherapy have been developed in the last years in order to increase the safety and efficacy of allergenic vaccines. In that way, different and modern vaccines have been prepared including more purified products such as depigmented allergen extracts; allergoids, consisting on big molecules of thousands of kDa, which contain all the individual allergens and show a significant decrease in severe adverse reactions; peptides or small aminoacid sequences; recombinant allergens; hypoallergenic vaccines where the IgE binding sites have been modified; or allergen-CpG fusion molecules. New presentations are under study and new treatments will be developed in the near future with the objective that the prevention of allergic disease may become a reality. The review article also discuss recent patent related to the field. PMID:19075996

  9. New routes for allergen immunotherapy

    OpenAIRE

    Johansen, Pål; von Moos, Seraina; Mohanan, Deepa; Kündig, Thomas M.; Senti, Gabriela

    2012-01-01

    IgE-mediated allergy is a highly prevalent disease in the industrialized world. Allergen-specific immunotherapy (SIT) should be the preferred treatment, as it has long lasting protective effects and can stop the progression of the disease. However, few allergic patients choose to undergo SIT, due to the long treatment time and potential allergic adverse events. Since the beneficial effects of SIT are mediated by antigen presenting cells inducing Th1, Treg and antibody responses, whereas the a...

  10. Antibody Peptide Based Antifungal Immunotherapy

    OpenAIRE

    Magliani, Walter; Conti, Stefania; Giovati, Laura; Zanello, Pier Paolo; Sperindè, Martina; Ciociola, Tecla; Polonelli, Luciano

    2012-01-01

    Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast kill...

  11. The immunotherapy of Alzheimer's disease

    OpenAIRE

    Weksler Marc E

    2004-01-01

    Abstract Only a small percentage of patients with Alzheimer's disease benefit from current drug therapy and for only a relatively short time. This is not surprising as the goal of these drugs is to enhance existing cerebral function in Alzheimer patients and not to block the progression of cognitive decline. In contrast, immunotherapy is directed at clearing the neurotoxic amyloid beta peptide from the brain that directly or indirectly leads to cognitive decline in patients with Alzheimer's d...

  12. The future of sublingual immunotherapy.

    Science.gov (United States)

    Marcucci, F; Duse, M; Frati, F; Incorvaia, C; Marseglia, G L; La Rosa, M

    2009-01-01

    Sublingual immunotherapy (SLIT) is currently the most prescribed form of allergen immunotherapy in many European countries. Its use has been accepted in the international consensus publications, and recently also the scepticism of USA scientists is attenuated. Still, this treatment may be improved, and the possible developments consist of modification of the materials, use of adjuvants and use of recombinant allergens. Moreover, new applications of SLIT, such as food allergy, seem promising. Concerning materials, the future form of SLIT is likely to be represented by tablets, which were already tested for efficacy and safety with grass pollen extracts, and are likely to increase the convenience for the patient by the use of no-updosing schedule. Adjuvants fitting with the characteristics of SLIT seem to be CpG oligodeoxynucleotides (CpG), able to interact with the Toll-like receptor 9 (TLR9) whose activation induces a Th1-like pattern of cytokine release, combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3-Dex), and Lactobacillus plantarum. The approach with recombinant allergens, named component-resolved diagnosis, offers the possibility to tailor immunotherapy, which was found to be effective in two randomized trials of subcutaneous SIT (16-17), while studies with SLIT are not yet available. Regarding food allergy, an important controlled study demonstrated that SLIT with hazelnut is able to increase patients tolerance over possible reactions from inadvertent assumption of the culprit food, and warrants for further trials with other foods. PMID:19944008

  13. Novel immunotherapies in lymphoid malignancies.

    Science.gov (United States)

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE(®)) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  14. Biologic Therapy (Immunotherapy) for Kidney Cancer

    Science.gov (United States)

    ... for kidney cancer Targeted therapies for kidney cancer Biologic therapy (immunotherapy) for kidney cancer Chemotherapy for kidney cancer Pain control for kidney cancer Treatment choices by stage for ...

  15. Effects of sublingual immunotherapy on allergic inflammation: an update.

    Science.gov (United States)

    Yacoub, Mona-Rita; Colombo, Giselda; Marcucci, Francesco; Caminati, Marco; Sensi, Laura; Di Cara, Giuseppe; Frati, Franco; Incorvaia, Cristoforo

    2012-08-01

    The most common allergic diseases, and especially the respiratory disorders such as rhinitis and asthma, are closely related to the allergic inflammation elicited by the causative allergen. This makes inflammation the main target of anti-allergic therapies. Among the available treatments, allergen specific immunotherapy (AIT) has a patent effect on allergic inflammation, which persists also after its discontinuation, and is the only therapy able to modify the natural history of allergy. The traditional, subcutaneous route of administration was demonstrated to modify the allergen presentation by dendritic cells (DCs) that in turn correct the phenotype of allergen-specific T cells, switching from the Th2-type response, typical of allergic inflammation and characterized by the production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines to a Th1-type response. This immune deviation is related to an increased IFN-gamma and IL-2 production as well as to the anergy of Th2 or to tolerance, the latter being related to the generation of allergen-specific T regulatory (Treg) cells, which produce cytokines such as IL-10 and TGF-beta. Anti-inflammatory mechanisms observed during sublingual AIT with high allergen doses proved to be similar to subcutaneous immunotherapy. Data obtained from biopsies clearly indicate that the pathophysiology of the oral mucosa, with particular importance for mucosal DCs, plays a crucial role in inducing tolerance to the administered allergen. PMID:22506880

  16. HEAT SHOCK PROTEIN gp96 AND CANCER IMMUNOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    岳培彬; 杨树德; 黄常志

    2002-01-01

    Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum.It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo and in vitro. Recent studies have indicated that gp96 molecules participate in major histocompatibility complex class I - restricted antigen presentation pathway. Immunization of mice with gp96 preparations isolated from cancer cells can elicit a cancer - specific protective T cell immune response that is recallable, which is a prerequisite for gp96 as a therapeutic vaccine against cancers. The immunogenicity of gp96 molecules has been attributed to the antigenic peptides associated with them. These phenomena provide a new pathway for cancer immunotherapy. The mechanism that the gp96 -peptide complex induces specific immune response and the explorations for gp96 - peptide complex as a therapeutic cancer vaccine are reviewed.

  17. A microfluidic approach towards hybridoma generation for cancer immunotherapy.

    Science.gov (United States)

    Lu, Yen-Ta; Pendharkar, Gaurav Prashant; Lu, Chung-Huan; Chang, Chia-Ming; Liu, Cheng-Hsien

    2015-11-17

    Dendritic cells/tumor fusions have shown to elicit anti-cancer immunity in different cancer types. However, the application of these vaccines for human cancer immunotherapy are limited by the instable quality and insufficient quanity of fusion cells. We present a cell electrofusion chip fabricated using soft lithography technique, which combines the rapid and precise cell pairing microstructures and the high yield electrofusion micro-electrodes to improve the cell fusion. The design uses hydrodynamic trapping in combination with positive dielectrophoretic force (pDEP) to achieve cell fusion. The chip consists of total 960 pairs of trapping channels, which are capable of pairing and fusing both homogeneous and heterogeneous types of cells. The fused cells can be easily taken out of the chip that makes this device a distinguishable from other designs. We observe pairing efficiency of 68% with fusion efficiency of 64%. PMID:26462149

  18. Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward?

    Directory of Open Access Journals (Sweden)

    Joanie Del Bano

    2015-12-01

    Full Text Available As evidenced by the recent approvals of Removab (EU, Trion Pharma in 2009 and of Blincyto (US, Amgen in 2014, the high potential of bispecific antibodies in the field of immuno-oncology is eliciting a renewed interest from pharmaceutical companies. Supported by rapid advances in antibody engineering and the development of several technological platforms such as Triomab or bispecific T cell engagers (BiTEs, the “bispecifics” market has increased significantly over the past decade and may occupy a pivotal space in the future. Over 30 bispecific molecules are currently in different stages of clinical trials and more than 70 in preclinical phase. This review focuses on the clinical potential of bispecific antibodies as immune effector cell engagers in the onco-immunotherapy field. We summarize current strategies targeting various immune cells and their clinical interests. Furthermore, perspectives of bispecific antibodies in future clinical developments are addressed.

  19. Mechanisms of immunotherapy to aeroallergens.

    Science.gov (United States)

    Shamji, M H; Durham, S R

    2011-09-01

    Allergen immunotherapy is allergen-specific, allergen dose- and time-dependent and is associated with long-term clinical and immunological tolerance that persists for years after discontinuation. Successful immunotherapy is accompanied by the suppression of numbers of T-helper 2 (Th2) effector cells, eosinophils, basophils, c-kit+mast cells and neutrophils infiltration in target organs, induction of IL-10 and/or TGF-β+Treg cells and increases in 'protective' non-inflammatory blocking antibodies, particularly IgG4 and IgA2 subclasses with inhibitory activity. These events are accompanied by a reduction and/or a redirection of underlying antigen-specific Th2-type T cell-driven hypersensitivity to the allergen(s) used for therapy. This suppression occurs within weeks or months as a consequence of the appearance of a population of regulatory T cells that exert their effects by mechanisms involving cell-cell contact, but also by the release of cytokines such as IL-10 (increases IgG4) and TGF-β (increases specific IgA). The more delayed-in-time appearance of antigen-specific T-helper 1 responses and alternative mechanisms such as Th2 cell anergy and/or apoptosis may also be involved. The mechanisms of sublingual immunotherapy are similar to those following a subcutaneous administration of allergen, whereas it is likely that additional events following antigen presentation in the sublingual mucosa and regional lymph nodes are involved. These insights have resulted in novel approaches and portend future biomarkers that may be surrogate or predictive of the clinical response to treatment. PMID:21762223

  20. Oral Immunotherapy for Food Allergy.

    Science.gov (United States)

    Burbank, Allison J; Sood, Puja; Vickery, Brian P; Wood, Robert A

    2016-02-01

    Food allergy is a potentially life-threatening condition with no approved therapies, apart from avoidance and injectable epinephrine for acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which food-allergic patients consume gradually increasing quantities of the food to increase their threshold for allergic reaction. This therapy carries significant risk of allergic reactions. The ability of OIT to desensitize patients to particular foods is well-documented, although the ability to induce tolerance has not been established. This review focuses on recent studies for the treatment of food allergies such as cow's milk, hen's egg, and peanut. PMID:26617227

  1. Sublingual immunotherapy (SLIT)--indications, mechanism, and efficacy: Position paper prepared by the Section of Immunotherapy, Polish Society of Allergy.

    Science.gov (United States)

    Jutel, Marek; Bartkowiak-Emeryk, Małgorzata; Bręborowicz, Anna; Cichocka-Jarosz, Ewa; Emeryk, Andrzej; Gawlik, Radosław; Gonerko, Paweł; Rogala, Barbara; Nowak-Węgrzyn, Anna; Samoliński, Bolesław

    2016-01-01

    SLIT (sublingual immunotherapy,) induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy), with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50-100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1-3 years has been provided by the large scale double-blind, placebo-controlled (DBPC) trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis) in both children and adults sensitized to pollen allergens (trees, grass, Parietaria), house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 - 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization. PMID:27012173

  2. [Dendritic cells in cancer immunotherapy].

    Science.gov (United States)

    Gato, M; Liechtenstein, T; Blanco-Luquín, I; Zudaire, M I; Kochan, G; Escors, D

    2015-01-01

    Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities. PMID:26486534

  3. Allergen specific immunotherapy in nasobronchial allergy.

    Directory of Open Access Journals (Sweden)

    Joshi S

    2003-12-01

    Full Text Available BACKGROUND: More than one antigen has been used for immunotherapy of allergic disorders. So far less than five antigens have been employed with variable results. AIM: To evaluate effect of multiple antigens up to six in the immunotherapy of nasobronchial allergy. SETTING AND DESIGN: Based on clinical history, symptoms present for at least 3 years with set criteria of immunomodulation for asthma and rhinitis: documented IgE mediated asthma and rhinitis, failure in allergen avoidance and moderate to severe clinical manifestations. MATERIAL AND METHODS: Five hundred cases of various allergic disorders attending allergy clinic of Bombay hospital were screened. Allergen specific immunotherapy was initiated in 131 subjects (56 -rhinitis and 75 asthma with prior consent. Patients suffering from allergic disorders secondary to diseases or drug therapy were excluded. Multiple allergen immunotherapy was given at specific intervals up to a period of one year. Allergen extracts were prepared as per standard technique. For statistical analysis "students′t test" was used. RESULTS AND CONCLUSIONS: Significant improvement in PEFR, reduction in skin sensitivity to allergens used in immunotherapy formulation and symptomatic relief without any untoward reaction show that multiple allergen immunotherapy is as effective as monoallergen immunotherapy in nasobronchial allergy.

  4. 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.

  5. Immunotherapy of Metastases Enhances Subsequent Chemotherapy

    Science.gov (United States)

    Hanna, Michael G.; Key, Marc E.

    1982-07-01

    In many multimodal therapies of cancer, postsurgical chemotherapy is administered before immunotherapy for treatment of micrometastatic disease. This sequence may not be the most efficacious. Experiments in which strain 2 guinea pigs bearing syngeneic L10 hepatocarcinomas were given immunotherapy showed that infiltrating immune effector cells not only were tumoricidal but disrupted the characteristically compact structure of metastatic foci. When cytotoxic drugs were administered at the peak of this inflammatory response, the survival rate of the guinea pigs increased significantly. We conclude that postsurgical immunotherapy can enhance the effect of cytotoxic drugs administered subsequently.

  6. 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.

  7. [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. PMID:23568994

  8. Grass pollen immunotherapy: where are we now.

    Science.gov (United States)

    Würtzen, Peter A; Gupta, Shashank; Brand, Stephanie; Andersen, Peter S

    2016-04-01

    During allergen immunotherapy (AIT), the allergic patient is exposed to the disease-inducing antigens (allergens) in order to induce clinical and immunological tolerance and obtain disease modification. Large trials of grass AIT with highly standardized subcutaneous and sublingual tablet vaccines have been conducted to document the clinical effect. Induction of blocking antibodies as well as changes in the balance between T-cell phenotypes, including induction of regulatory T-cell subtypes, have been demonstrated for both treatment types. These observations increase the understanding of the immunological mechanism behind the clinical effect and may make it possible to use the immunological changes as biomarkers of clinical effect. The current review describes the recent mechanistic findings for subcutaneous immunotherapy and sublingual immunotherapy/tablet treatment and discusses how the observed immunological changes translate into a scientific foundation for the observed clinical effects of grass pollen immunotherapy and lead to new treatment strategies for grass AIT. PMID:26973122

  9. 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.

  10. Allergen specific immunotherapy in nasobronchial allergy.

    OpenAIRE

    Joshi S; Tripathi D; Dhar H

    2003-01-01

    BACKGROUND: More than one antigen has been used for immunotherapy of allergic disorders. So far less than five antigens have been employed with variable results. AIM: To evaluate effect of multiple antigens up to six in the immunotherapy of nasobronchial allergy. SETTING AND DESIGN: Based on clinical history, symptoms present for at least 3 years with set criteria of immunomodulation for asthma and rhinitis: documented IgE mediated asthma and rhinitis, failure in allergen avoidance and modera...

  11. Melanoma immunotherapy dominates the field.

    Science.gov (United States)

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  12. Immunotherapy in Sarcoma: Future Horizons.

    Science.gov (United States)

    Burgess, Melissa; Gorantla, Vikram; Weiss, Kurt; Tawbi, Hussein

    2015-11-01

    Immunologic approaches to cancer are over a century old. Over the years, the strategy has been fine-tuned from inciting infections in subjects to inhibiting negative regulatory signals from the innate immune system. Sarcomas are among the first tumors to be considered for immune interventions. From Coley's toxin to cytokine-based therapies to adoptive cell therapy, there have been numerous immunotherapeutic investigations in this patient population. A promising strategy includes adoptive T cell therapy which has been studied in small cohorts of synovial sarcoma, a subtype that is known to widely express the cancer testis antigen, NY-ESO-1. Additionally, recent data in metastatic melanoma and renal cell carcinoma demonstrate the utility and tremendous efficacy of immune checkpoint blockade with increased rates of durable responses compared to standard therapies. Responses in traditionally "non-immunogenic" tumors, such as lung and bladder cancers, provide ample rationale for the study of immune checkpoint inhibitors in sarcoma. While immunotherapy has induced some responses in sarcomas, further research will help clarify optimal patient selection for future clinical trials and new combinatorial immunotherapeutic strategies. PMID:26423769

  13. Mechanisms of subcutaneous allergen immunotherapy.

    Science.gov (United States)

    Soyer, Ozge U; Akdis, Mubeccel; Akdis, Cezmi A

    2011-05-01

    Allergen-specific immunotherapy (SIT) is the only curative approach in the treatment of allergic diseases defined up-to-date. Peripheral T-cell tolerance to allergens, the goal of successful allergen-SIT, is the primary mechanism in healthy immune responses to allergens. By repeated administration of increased doses of the causative allergen, allergen-SIT induces a state of immune tolerance to allergens through the constitution of T regulatory (Treg) cells, including allergen-specific interleukin (IL)-10-secreting Treg type 1 cells and CD4(+)CD25(+)Treg cells; induction of suppressive cytokines, such as IL-10 and transforming growth factor β; suppression of allergen-specific IgE and induction of IgG4 and IgA; and suppression of mast cells, basophils, eosinophils, and inflammatory dendritic cells. This review summarizes the current knowledge on the mechanisms of allergen-SIT with emphasis on the roles of Treg cells in allergen-SIT. PMID:21530813

  14. New routes for allergen immunotherapy.

    Science.gov (United States)

    Johansen, Pål; von Moos, Seraina; Mohanan, Deepa; Kündig, Thomas M; Senti, Gabriela

    2012-10-01

    IgE-mediated allergy is a highly prevalent disease in the industrialized world. Allergen-specific immunotherapy (SIT) should be the preferred treatment, as it has long lasting protective effects and can stop the progression of the disease. However, few allergic patients choose to undergo SIT, due to the long treatment time and potential allergic adverse events. Since the beneficial effects of SIT are mediated by antigen presenting cells inducing Th1, Treg and antibody responses, whereas the adverse events are caused by mast cells and basophils, the therapeutic window of SIT may be widened by targeting tissues rich in antigen presenting cells. Lymph nodes and the epidermis contain high density of dendritic cells and low numbers of mast cells and basophils. The epidermis has the added benefit of not being vascularised thereby reducing the chances of anaphylactic shock due to leakage of allergen. Hence, both these tissues represent highly promising routes for SIT and are the focus of discussion in this review. PMID:23095873

  15. Immunotherapy in renal cell carcinoma.

    Science.gov (United States)

    Bukowski, R M

    1999-06-01

    Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy include the observations of spontaneous tumor regression, the presence of a T-cell-mediated immune response, and the tumor responses observed in patients receiving cytokine therapy. Analysis of prognostic factors in these patients demonstrates that clinical responses occur most frequently in individuals with good performance status. The cytokines interleukin-2 (IL-2, aldesleukin [Proleukin], interferon-alfa (Intron A, Roferon-A), or the combination produce responses in 15% to 20% of patients. Randomized trials suggest that administration of interferon-alfa may result in a modest improvement in median survival. Investigation of the molecular genetics of renal cell carcinoma and the presence of T-lymphocyte immune dysregulation have suggested new therapeutic strategies. Further preclinical and clinical studies investigating inhibitors of angiogenesis or pharmacologic methods to reverse immune dysregulation are ongoing. Therapeutic results in patients with renal cell carcinoma remain limited, and investigational approaches are warranted. PMID:10378218

  16. 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

  17. Current Studies of Immunotherapy on Glioblastoma.

    Science.gov (United States)

    Agrawal, Neena Stephanie; Miller, Rickey; Lal, Richa; Mahanti, Harshini; Dixon-Mah, Yaenette N; DeCandio, Michele L; Vandergrift, W Alex; Varma, Abhay K; Patel, Sunil J; Banik, Naren L; Lindhorst, Scott M; Giglio, Pierre; Das, Arabinda

    2014-04-01

    Glioblastoma is a form of brain tumor with a very high morbidity and mortality. Despite decades of research, the best treatments currently in clinical practice only extend survival by a number of months. A promising alternative to conventional treatment for glioblastomas is immunotherapy. Although proposed over a century ago, the field of cancer immunotherapy has historically struggled to translate it into effective clinical treatments. Better understanding is needed of the various regulatory and co-stimulatory factors in the glioblastoma patient for more efficient immunotherapy treatments. The tumor microenvironment is anatomically shielded from normal immune-surveillance by the blood-brain barrier, irregular lymphatic drainage system, and it's in a potently immunosuppressive environment. Immunotherapy can potentially manipulate these forces effectively to enhance anti-tumor immune response and clinical benefit. New treatments utilizing the immune system show promise in terms of targeting and efficacy. This review article attempts to discuss current practices in glioblastoma treatment, the theory behind immunotherapy, and current research into various clinical trials. PMID:25346943

  18. Cost-minimization analysis of sublingual immunotherapy versus subcutaneous immunotherapy for house dust mite respiratory allergic disease in Denmark.

    Science.gov (United States)

    Rønborg, Steen; Johnsen, Claus R; Theilgaard, Sune; Winther, Anders; Hahn-Pedersen, Julie; Andreasen, Jakob Nørgaard; Olsen, Jens

    2016-08-01

    Objectives Currently, patients with persistent moderate-to-severe house dust mite (HDM) allergic rhinitis despite use of symptom-relieving medication can be offered subcutaneously administered allergy immunotherapy (SQ SCIT; Alutard SQ) as standard care of treatment in Denmark. Recently, a HDM sublingually administered allergy immunotherapy tablet (SQ SLIT-tablet; ACARIZAX) has been developed for at-home treatment. The purpose of this analysis is to compare the costs related to treatment and administration of SQ SLIT-tablet and SQ SCIT. Methods Assuming equal efficacy between ther SQ SLIT-tablet and SQ SCIT, the cost-minimization analysis was the most appropriate for the comparison. According to guidelines and Summary of Product Characteristics, the treatment duration of SQ SLIT-tablet is 3 years and 3-5 years for SQ SCIT. The courses of treatment vary among patients and, therefore, the costs of treatment have been calculated for an average patient with HDM respiratory allergic disease (RAD) receiving either SQ SLIT-tablet or SQ SCIT. All costs associated with allergy immunotherapy were collected, i.e., cost of medication, administration and treatment setting, and discounted according to Danish guidelines. Comprehensive univariate sensitivity analyses were carried out. Results The treatment costs for an average patient with HDM RAD are €3094 for SQ SLIT-tablet and €3799 for SQ SCIT; however, when adding indirect costs to the calculations the total costs of the treatments are €3697 and €6717 for SQ SLIT-tablet and SQ SCIT, respectively. Therefore, if 2500 patients with HDM RAD were treated with SQ SLIT-tablet instead of SQ SCIT, it would elicit a saving to the healthcare system of ∼€1.8 million. The conclusion was robust to any changes in the sensitivity analysis. Conclusion With regards to the cost of treating Danish patients with HDM RAD, it is clearly cost-saving to treat patients with SQ SLIT-tablet compared to SQ SCIT. PMID:26909663

  19. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

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

    2014-01-01

    cancer immunotherapies has yet to be fulfilled. The insufficient efficacy of existing treatments can be attributed to a number of biological and technical issues. In this review, we detail the current limitations of immunotherapy target selection and design, and review computational methods to streamline......The mechanisms of immune response to cancer have been studied extensively and great effort has been invested into harnessing the therapeutic potential of the immune system. Immunotherapies have seen significant advances in the past 20 years, but the full potential of protective and therapeutic...... and co-targets for single-epitope and multi-epitope strategies. We provide examples of application to the well-known tumor antigen HER2 and suggest bioinformatics methods to ameliorate therapy resistance and ensure efficient and lasting control of tumors....

  20. 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....

  1. Strategies of mucosal immunotherapy for allergic diseases

    Institute of Scientific and Technical Information of China (English)

    Yi-Ling Ye; Ya-Hui Chuang; Bor-Luen Chiang

    2011-01-01

    Incidences of allergic disease have recently increased worldwide.Allergen-specific immunotherapy (SIT) has long been a controversial treatment for allergic diseases.Although beneficial effects on clinically relevant outcomes have been demonstrated in clinical trials by subcutaneous immunotherapy (SCIT),there remains a risk of severe and sometimes fatal anaphylaxis.Mucosal immunotherapy is one advantageous choice because of its non-injection routes of administration and lower side-effect profile.This study reviews recent progress in mucosal immunotherapy for allergic diseases.Administration routes,antigen quality and quantity,and adjuvants used are major considerations in this field.Also,direct uses of unique probiotics,or specific cytokines,have been discussed.Furthermore,some researchers have reported new therapeutic ideas that combine two or more strategies.The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation,which includes continuous searching for efficient adjuvants,collecting more information about dominant T-cell epitopes of allergens,and having the proper combination of each.In clinics,when compared to other mucosal routes,sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration,although local and systemic side effects have been reported.Additionally,not every allergen has the same beneficial effect.Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults.Data collected from large,well-designed,double-blind,placebo-controlled,and randomized trials,with post-treatment follow-up,can provide robust substantiation of current evidence.

  2. Elicitation of ostomy pouch preferences

    DEFF Research Database (Denmark)

    Bonnichsen, Ole

    2011-01-01

    stoma care would affect patients and, to the author's knowledge, the present study is the first to elicit preferences for potential improvements in ostomy pouches in the form of monetary values. Objective: This article examines and measures Swedish patients' preferences for potential improvements in...... the utility that patients would obtain from a potential improvement in their ostomy pouch. This provides information as to how treatment options in terms of stoma management can be structured so as to maximize the benefits for patients....

  3. Survey Based Reviewof Elicitation Problems

    OpenAIRE

    Sidra Arshad

    2016-01-01

    Any software development process is the combination of multiple development activities and each activity has a vital role in the software development cycle. Requirement Engineering is the main and basic branch of Software Engineering, it has many phases but the most initial phase is Requirement Elicitation. In this phase requirements are gathered for system development. This paper provides a literature review of the requirements engineering processes performed in traditional and ...

  4. Effect of SPG (Sonifilan) immunotherapy and PDT on murine tumor

    International Nuclear Information System (INIS)

    PhotoDynamic Therapy of solid tumors is unique in eliciting a strong host immune response unparalleled in other cancer therapies. This immune response is manifested as an acute inflammatory reaction, and can be readily seen as redness and edema around the treated area. Destruction of typical solid tumor cannot be accomplished solely by direct phototoxic action. This was shown to be the case even with drugs more potent in this direct killing effect than Photofrin, the photosensitizer presently used in clinical PDT. Limiting factors seem to be regional insufficiencies in supply of molecular oxygen, needed for generation of phototoxic species. They can be ascribed to the existence of chronically and acute hypoxic tumor regions, oxygen consumption by the photodynamic process, and vascular shutdown induced during PDT. The remaining tumor mass is eradicated by an indirect effect, necrosis induced by destruction of tumor vasculature. Since most events in PDT treated tumor that lead to vascular collapse are, in fact, typical inflammatory manifestations, it was suggested that PDT-induced acute inflammatory reaction actually leads to vascular damage. In a related report characteristics are shown of cellular inflammatory infiltrate in PDT-treated murine tumor. This work examines the effect of combining PDT with immunotherapy, in an attempt to investigate a possibility of amplification of immune reaction to PDT and its direction towards more pervasive destruction of treated tumors. (authors). 6 refs

  5. A mouse model for HBV immunotolerance and immunotherapy.

    Science.gov (United States)

    Yang, Dan; Liu, Longchao; Zhu, Danming; Peng, Hua; Su, Lishan; Fu, Yang-Xin; Zhang, Liguo

    2014-01-01

    Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus (HBV) infection. In this study, we report a mouse model with sustained HBV viremia after infection with a recombinant adeno-associated virus (AAV) carrying a replicable HBV genome (AAV/HBV). Similar to the clinical HBV carriers, the mice infected with AAV/HBV were sero-negative for antibodies against HBV surface antigen (HBsAg). Immunization with the conventional HBV vaccine in the presence of aluminum adjuvant failed to elicit an immune response against HBV in these mice. To identify a vaccine that can potentially circumvent this tolerance, the TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with HBsAg/CpG induced not only clearance of viremia, but also strong antibody production and T-cell responses. Furthermore, both the DNA replication and protein expression of HBV were significantly reduced in the livers of AAV/HBV-infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model for investigating the underlying mechanism(s) of HBV immunotolerance and for developing novel immunotherapies to eradicate HBV infections. PMID:24076617

  6. Mechanisms of immunotherapy to wasp and bee venom.

    Science.gov (United States)

    Ozdemir, C; Kucuksezer, U C; Akdis, M; Akdis, C A

    2011-09-01

    Hymenoptera venoms are important allergens that can elicit both local and systemic allergic reactions, including life-threatening anaphylaxis. Venom immunotherapy (VIT) remains the most effective treatment, reducing the risk of systemic reactions in individuals with Hymenoptera venom allergy. VIT can restore normal immunity against venom allergens and provide patients with a lifetime of tolerance to venoms. During VIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T (Treg) cells, which suppress proliferative and cytokine responses against the venom allergens. Treg cells are characterized by IL-10 secretion that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Treg cells also have influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies against venom allergens. An accumulating body of evidence suggests that Treg cells may affect allergen sensitization and methods for enhancing this cell population may eventually improve the efficacy of VIT. In this article, immune mechanisms enrolled in bee and wasp VIT are reviewed. PMID:21729181

  7. Role of IL-2 in cancer immunotherapy.

    Science.gov (United States)

    Jiang, Tao; Zhou, Caicun; Ren, Shengxiang

    2016-06-01

    Interleukin-2 (IL-2) is one of the key cytokines with pleiotropic effects on immune system. It has been approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma. Recent progress has been made in our understanding of IL-2 in regulating lymphocytes that has led to exciting new directions for cancer immunotherapy. While improved IL-2 formulations might be used as monotherapies, their combination with other anticancer immunotherapies, such as adoptive cell transfer regimens, antigen-specific vaccination, and blockade of immune checkpoint inhibitory molecules, for example cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) mono-antibodies, would held the promise of treating metastatic cancer. Despite the comprehensive studies of IL-2 on immune system have established the application of IL-2 for cancer immunotherapy, a number of poignant obstacles remain for future research. In the present review, we will focus on the key biological features of IL-2, current applications, limitations, and future directions of IL-2 in cancer immunotherapy. PMID:27471638

  8. Sublingual Immunotherapy for Allergic Fungal Sinusitis.

    Science.gov (United States)

    Melzer, Jonathan M; Driskill, Brent R; Clenney, Timothy L; Gessler, Eric M

    2015-10-01

    Allergic fungal sinusitis (AFS) is a condition that has an allergic basis caused by exposure to fungi in the sinonasal tract leading to chronic inflammation. Despite standard treatment modalities, which typically include surgery and medical management of allergies, patients still have a high rate of recurrence. Subcutaneous immunotherapy (SCIT) has been used as adjuvant treatment for AFS. Evidence exists to support the use of sublingual immunotherapy (SLIT) as a safe and efficacious method of treating allergies, but no studies have assessed the utility of SLIT in the management of allergic fungal sinusitis. A record review of cases of AFS that are currently or previously treated with sublingual immunotherapy from 2007 to 2011 was performed. Parameters of interest included serum IgE levels, changes in symptoms, Lund-McKay scores, decreased sensitization to fungal allergens associated with AFS, and serum IgE levels. Ten patients with diagnosed AFS were treated with SLIT. No adverse effects related to the use of SLIT therapy were identified. Decreases in subjective complaints, exam findings, Lund-McKay scores, and serum IgE levels were observed. Thus, sublingual immunotherapy appears to be a safe adjunct to the management of AFS that may improve patient outcomes. PMID:25902841

  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. Topical immunotherapy with diphenylcyclopropenone-induced vitiligo.

    Science.gov (United States)

    Kutlubay, Zekayi; Engin, Burhan; Songur, Abdullah; Serdaroglu, Server; Tuzun, Yalcin

    2016-08-01

    Topical immunotherapy made by diphenylcyclopropenone (DPCP) is an alternative treatment that can be used safely and efficaciously in recalcitrant alopecia areata patients. DPCP-induced vitiligo is a rare, but documented, unwanted side effect. The real mechanism of DPCP-induced vitiligo is not well known. PMID:26963903

  11. 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. PMID:25459121

  12. Eliciting expert knowledge in conservation science.

    Science.gov (United States)

    Martin, Tara G; Burgman, Mark A; Fidler, Fiona; Kuhnert, Petra M; Low-Choy, Samantha; McBride, Marissa; Mengersen, Kerrie

    2012-02-01

    Expert knowledge is used widely in the science and practice of conservation because of the complexity of problems, relative lack of data, and the imminent nature of many conservation decisions. Expert knowledge is substantive information on a particular topic that is not widely known by others. An expert is someone who holds this knowledge and who is often deferred to in its interpretation. We refer to predictions by experts of what may happen in a particular context as expert judgments. In general, an expert-elicitation approach consists of five steps: deciding how information will be used, determining what to elicit, designing the elicitation process, performing the elicitation, and translating the elicited information into quantitative statements that can be used in a model or directly to make decisions. This last step is known as encoding. Some of the considerations in eliciting expert knowledge include determining how to work with multiple experts and how to combine multiple judgments, minimizing bias in the elicited information, and verifying the accuracy of expert information. We highlight structured elicitation techniques that, if adopted, will improve the accuracy and information content of expert judgment and ensure uncertainty is captured accurately. We suggest four aspects of an expert elicitation exercise be examined to determine its comprehensiveness and effectiveness: study design and context, elicitation design, elicitation method, and elicitation output. Just as the reliability of empirical data depends on the rigor with which it was acquired so too does that of expert knowledge. PMID:22280323

  13. Workshop on immunotherapy combinations. Society for immunotherapy of cancer annual meeting Bethesda, November 3, 2011

    Directory of Open Access Journals (Sweden)

    Forero Ivan

    2012-05-01

    Full Text Available Abstract Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1 the most promising combinations found in the laboratory; 2 early success of combination immunotherapy in clinical trials; 3 industry perspectives on combination approaches, and 4 relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and “perceived” business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer

  14. Workshop on immunotherapy combinations. Society for Immunotherapy of Cancer annual meeting Bethesda, November 3, 2011.

    Science.gov (United States)

    Martinez Forero, Ivan; Okada, Hideho; Topalian, Suzanne L; Gajewski, Thomas F; Korman, Alan J; Melero, Ignacio

    2012-01-01

    Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1) the most promising combinations found in the laboratory; 2) early success of combination immunotherapy in clinical trials; 3) industry perspectives on combination approaches, and 4) relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and "perceived" business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace. PMID

  15. Eliciting Spill: A methodological note

    Directory of Open Access Journals (Sweden)

    Alvita Nathaniel, Ph.D.

    2008-03-01

    Full Text Available Classic grounded theory is an inductive process that focuses on the experiences and perceptions of research participants (Glaser, 1978, 1998. Although grounded theorists may utilize other types of data, most are likely to gather information through qualitative interviews. The theorist seeks to understand what is going on as people resolve their main concern in a given substantive area. People know what is important to them and most want to tell their stories. They feel encouraged to talk when they recognize that their stories are valued. Once the informant realizes that he or she is being heard, the story flows. This is what Glaser refers to as “spill.” When this occurs, the theorist becomes a vessel to receive the story. As Glaser describes it, “The researcher will become a ‘big ear’ to pour into incessantly” (1998, p. 124. But, as easy as this seems, the researcher must overcome certain positivist tendencies to allow this to happen. Rather than asking a list of pre-planned questions, the grounded theorist will try to develop one question that will trigger the telling of a story. Eliciting spill requires a deliberate process that employs a deep understanding of the fundamentals of classic grounded theory. Derived from Glaser’s writings, the following are suggestions intended to help the novice grounded theorist to elicit spill.

  16. 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.

  17. Cripto-1 vaccination elicits protective immunity against metastatic melanoma

    Science.gov (United States)

    Ligtenberg, M. A.; Witt, K.; Galvez-Cancino, F.; Sette, A.; Lundqvist, A.; Lladser, A.; Kiessling, R.

    2016-01-01

    ABSTRACT Metastatic melanoma is a fatal disease that responds poorly to classical treatments but can be targeted by T cell-based immunotherapy. Cancer vaccines have the potential to generate long-lasting cytotoxic CD8+ T cell responses able to eradicate established and disseminated tumors. Vaccination against antigens expressed by tumor cells with enhanced metastatic potential represents a highly attractive strategy to efficiently target deadly metastatic disease. Cripto-1 is frequently over-expressed in human carcinomas and melanomas, but is expressed only at low levels on normal differentiated tissues. Cripto-1 is particularly upregulated in cancer-initiating cells and is involved in cellular processes such as cell migration, invasion and epithelial–mesenchymal transition, which are hallmarks of aggressive cancer cells able to initiate metastatic disease. Here, we explored the potential of Cripto-1 vaccination to target metastatic melanoma in a preclinical model. Cripto-1 was overexpressed in highly metastatic B16F10 cells as compared to poorly metastatic B16F1 cells. Moreover, B16F10 cells grown in sphere conditions to enrich for cancer stem cells (CSC) progressively upregulated cripto1 expression. Vaccination of C57Bl/6 mice with a DNA vaccine encoding mouse Cripto-1 elicited a readily detectable/strong cytotoxic CD8+ T cell response specific for a H-2 Kb-restricted epitope identified based on its ability to bind H-2b molecules. Remarkably, Cripto-1 vaccination elicited a protective response against lung metastasis and subcutaneous challenges with highly metastatic B16F10 melanoma cells. Our data indicate that vaccination against Cripto-1 represents a novel strategy to be tested in the clinic.

  18. Development of PROSTVAC immunotherapy in prostate cancer.

    Science.gov (United States)

    Singh, Parminder; Pal, Sumanta K; Alex, Anitha; Agarwal, Neeraj

    2015-01-01

    PROSTVAC immunotherapy is a heterologous prime-boost regimen of two different recombinant pox-virus vectors; vaccinia as the primary immunotherapy, followed by boosters employing fowlpox, to provoke immune responses against prostate-specific antigen. Both vectors contain transgenes for prostate-specific antigen and a triad of T-cell costimulatory molecules (TRICOM). In a placebo-controlled Phase II trial of men with minimally symptomatic, chemotherapy-naive metastatic castration-resistant prostate cancer, PROSTVAC was well tolerated and associated with a 44% reduction in death. With a novel mechanism of action, and excellent tolerability, PROSTVAC has the potential to dramatically alter the treatment landscape of prostate cancer, not only as a monotherapy, but also in combination with other novel agents, such as immune check point inhibitors and novel androgen receptor blockers. A Phase III trial recently completed accrual. PMID:26235179

  19. Coinhibitory Pathways in Immunotherapy for Cancer.

    Science.gov (United States)

    Baumeister, Susanne H; Freeman, Gordon J; Dranoff, Glenn; Sharpe, Arlene H

    2016-05-20

    The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors exploit these coinhibitory pathways to evade immune eradication. Blockade of the PD-1 and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients with a variety of tumor types, and additional combinations are further improving response rates. In this review we discuss the immunoregulatory functions of coinhibitory pathways and their translation to effective immunotherapies for cancer. PMID:26927206

  20. Generation of IgE-based immunotherapies against HER-2 overexpressing tumours

    International Nuclear Information System (INIS)

    same specificity as the original trastuzumab IgG. Moreover, a three-colour flow cytometric assay indicated that even though both antibodies were able to induce tumour cell killing, they used different mechanisms: trastuzumab IgG acted via antibody-dependent cell-mediated phagocytosis (ADCP), whereas trastuzumab IgE elicited mostly antibody-dependent cell-mediated cytotoxicity (ADCC). Based on the presented data we conclude that tumour-specific IgE, induced actively or applied in a passive manner, represents a potent alternative to IgG-based immunotherapies against cancer. (author)

  1. 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. PMID:27033211

  2. Local immunotherapy in experimental murine lung inflammation

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Caroline Uebel, Sonja Koch, Anja Maier, Nina Sopel, Anna Graser, Stephanie Mousset & Susetta Finotto ### Abstract Innovative local immunotherapy for severe lung diseases such as asthma, chronic obstructive pulmonary disease or lung cancer requires a successful delivery to access the desired cellular target in the lung. An important route is the direct instillation into the airways in contrast to delivery through the digestive tract. This protocol details a method to deliv...

  3. Adoptive immunotherapy for cancer: building on success

    OpenAIRE

    Gattinoni, Luca; Powell, Daniel J.; Rosenberg, Steven A.; Restifo, Nicholas P

    2006-01-01

    Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic environment enables tumour-reactive T cells to destroy large burdens of metastatic tumour and how the state of differentiation of the adoptively transferred T cells can affect the outcome of treatment. We also discuss how the translation of these new findings might further improve the efficacy of adoptive cell transfer through the u...

  4. Multivalent glycomimetics in experimental anticancer immunotherapy

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca; Pospíšil, Miloslav; Krist, Pavel; Křen, Vladimír; Huliková, Katarína; Luptovcová, Martina; Svoboda, Jan; Kuldová, Markéta; Bezouška, Karel; Rossmann, Pavel; Difato, Francesco; Mosca, F.; Fišerová, Anna

    Praha : Blackwell Publishing, 2006, s. 51-51. [Annual Meeting of the European Society for Clinical Investigation /40./. Prague (CZ), 15.03.2006-18.03.2006] R&D Projects: GA ČR GA524/04/0102; GA AV ČR IAA500200509 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50110509 Keywords : immunotherapy * lectin-like receptors Subject RIV: EE - Microbiology, Virology

  5. Molecular biomarkers for grass pollen immunotherapy

    OpenAIRE

    Popescu, Florin-Dan

    2014-01-01

    Grass pollen allergy represents a significant cause of allergic morbidity worldwide. Component-resolved diagnosis biomarkers are increasingly used in allergy practice in order to evaluate the sensitization to grass pollen allergens, allowing the clinician to confirm genuine sensitization to the corresponding allergen plant sources and supporting an accurate prescription of allergy immunotherapy (AIT), an important approach in many regions of the world with great plant biodiversity and/or wher...

  6. Allergen-Specific Immunotherapy in Food Anaphylaxis

    OpenAIRE

    Kerzl, Regina; Mempel, Martin; Ring, Johannes

    2008-01-01

    Specific immunotherapy (SIT) protocols for nutritional allergens have only recently been established with a focus on oral allergy syndrome because of pollen cross-reacting antibodies. For these patients, a substantial number of studies have been published suggesting benefits from SIT. The situation in true anaphylaxis to food allergens such as peanut allergy is more complex, and therapeutic strategies are based on individual protocols rather than controlled studies. However, in defined cases,...

  7. Prostate cancer immunotherapy: beyond immunity to curability.

    Science.gov (United States)

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials. PMID:25367978

  8. Immunotherapy: A useful strategy to help combat multidrug resistance

    OpenAIRE

    Curiel, Tyler J.

    2012-01-01

    Multidrug resistance (MDR) renders cancer cells relatively invulnerable to treatment with many standard cytotoxic anti-cancer agents. Cancer immunotherapy could be an important adjunct other strategies to treat MDR positive cancers, as resistance to immunotherapy generally is unrelated to mechanisms of resistance to cytotoxic agents. Immunotherapy to combat MDR positive tumors could use any of the following strategies: direct immune attack against MDR positive cells, using MDR as an immune ta...

  9. Review on Immunotherapies for Lung Cancer

    Directory of Open Access Journals (Sweden)

    Sha JIN

    2012-10-01

    Full Text Available Lung cancer is a highly malignant disease with poor prognosis, most cases are diagnosed at a very late stage. More effective medications or therapies should be developed to improve its prognosis. The advancement of tumor immunity and tumor immunosuppression facilitated the feasibility of immunotherapies for lung cancer. Ipilimumab, antibody to Programmed death-1 (PD-1, Toll-like receptor agonists, liposomal BLP25 (L- BLP25, belagenpumatucel-L, melanoma-associated antigen A3 (MAGE-A3 vaccine and talactoferrin have been proved to be effective for lung cancer through early clinical trials, most of the drugs have moved forward to phase III trials, so as to collect much higher level evidence to support the immunotherapies incorporated into the multidisciplinary treatment of lung cancer. The selection of target patients at appropriate stages, breaking down of tumor immunosuppression as well as the objective measurement of tumor response to the therapy are major challenges for the development of immunotherapies for lung cancer. The clarifying of the mechanism of immune escape led to the above drug development, and immune-senescence has already become the hotspot in this field.

  10. Laser immunotherapy of canine and feline neoplasia

    Science.gov (United States)

    Woods, J. P.; Bartels, Kenneth E.; Davidson, Ellen B.; Ritchey, Jerry W.; Lehenbauer, Terry W.; Nordquist, Robert E.; Chen, Wei R.

    1998-07-01

    The major cause of treatment failure in human and veterinary cancer patients is tumor invasion and metastasis. The inability of local therapy (surgery, radiation, photodynamic therapy) to eradicate a metastatic cancer presents a challenge in the therapy of residual or micrometastatic disease. Because of its local therapy limitations, chromophore-enhanced selective photothermal laser treatment has been augmented with a superimposed laser-induced systemic photobiological reaction, laser immunotherapy. Laser immunotherapy is a novel cancer treatment consisting of: (1) a laser in the infrared wavelength range (i.e. 805 nm solid state laser); (2) a photosensitizer of the corresponding absorption peak [i.e. indocyanine green (ICG)]; and (3) an immunoadjuvant [i.e. glycated chitosan gel (GCG)]. The intratumor injection of the photosensitizer (ICG) and immunoadjuvant (GCG) solution is followed by noninvasive laser irradiation. The laser energy causes tumor cell destruction by photothermal interaction to reduce the tumor burden and at the same time exposes tumor antigens. The immunoadjuvant concomitantly stimulates the host to mount a systemic anti-tumor immune response against the remaining cells of the tumor and to induce a long-term, tumor-specific immunity. This study investigates the feasibility of utilizing laser immunotherapy as an adjunctive therapy for the control of feline fibrosarcoma in future.

  11. 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. PMID:8526179

  12. Sublingual immunotherapy in children: facts and needs

    Directory of Open Access Journals (Sweden)

    Frati Franco

    2009-10-01

    Full Text Available Abstract Allergen specific immunotherapy (SIT is the practice of administering gradually increasing doses of the specific causative allergen to reduce the clinical reactivity of allergic subjects, and is the only treatment targeting the causes of hypersensitivity and not only the symptoms, as done by drugs. The traditional, subcutaneous immunotherapy (SCIT was burdened by the problem of systemic reactions which may be sometimes severe and - though very rarely - even fatal. This was the background to develop non injections routes for SIT and particularly sublingual immunotherapy (SLIT, that emerged as a real treatment option for respiratory allergy. A number of studies was conducted to evaluate efficacy and safety of SLIT, the first meta-analysis - including 22 placebo-controlled trials - concluded for positive results in both issues, but the number of studies on children was too low to draw definite conclusions. Since then, many other studies became available and make possible to analyze SLIT in children in its well defined aspects as well as in sides still requiring more solid data.

  13. Immunotherapy for nasopharyngeal cancer-a review.

    Science.gov (United States)

    Jain, Amit; Chia, Whay Kuang; Toh, Han Chong

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV) and characterized by peritumoral immune infiltrate. Advanced NPC has high lethality. Immunotherapy directed against EBV antigen targets has been previously explored in clinical trials, and is likely to be validated as an important target in NPC as randomized data emerges in the future. Cancer vaccines and adoptive T cell therapy have been explored in the clinic, with the latter showing the greatest success. Recent advances in gene sequencing technology now allow personalized tumor epitope mapping, whilst the advent of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis offers the opportunity to activate adaptive T cell response in vivo. Anti-PD1 antibodies have shown promising activity in early phase clinical trials, and randomized studies against chemotherapy are underway. As immunotherapy is incorporated into standard treatment paradigms, issues of optimal combinations with targeting agents, immune adjuvants, and sequence with chemotherapy and radiation therapy will need to be addressed. Effective strategies to increase tumor antigenicity, improve immunological memory and reduce immune escape, will need to be developed to improve treatment outcomes. Here we present a brief history of the evolution of immunotherapy in NPC, and highlight key concepts relevant to its further development in the clinic. PMID:27121882

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

    Science.gov (United States)

    Calderon, Moises A; Demoly, Pascal; Gerth van Wijk, Roy; Bousquet, Jean; Sheikh, Aziz; Frew, Anthony; Scadding, Glenis; Bachert, Claus; Malling, Hans J; Valenta, Rudolph; Bilo, Beatrice; Nieto, Antonio; Akdis, Cezmi; Just, Jocelyne; Vidal, Carmen; Varga, Eva M; Alvarez-Cuesta, Emilio; Bohle, Barbara; Bufe, Albrecht; Canonica, Walter G; Cardona, Victoria; Dahl, Ronald; Didier, Alain; Durham, Stephen R; Eng, Peter; Fernandez-Rivas, Montserrat; Jacobsen, Lars; Jutel, Marek; Kleine-Tebbe, Jörg; Klimek, Ludger; Lötvall, Jan; Moreno, Carmen; Mosges, Ralph; Muraro, Antonella; Niggemann, Bodo; Pajno, Giovanni; Passalacqua, Giovanni; Pfaar, Oliver; Rak, Sabina; Senna, Gianenrico; Senti, Gabriela; Valovirta, Erkka; van Hage, Marianne; Virchow, Johannes C; Wahn, Ulrich; Papadopoulos, Nikolaos

    2012-01-01

    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 which Europe is recognized as a

  15. 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

  16. Stem cells and cancer immunotherapy: Arrowhead’s 2nd annual cancer immunotherapy conference

    OpenAIRE

    Bot, Adrian; Chiriva-Internati, Maurizio; Cornforth, Andrew; Brian J Czerniecki; Ferrone, Soldano; Geles, Kenneth; Greenberg, Philip D.; Hurt, Elaine; Koya, Richard C.; Masoud H Manjili; Matsui, William; Morgan, Richard A.; Palena, Claudia M; Powell Jr, Daniel J; Restifo, Nicholas P

    2014-01-01

    Investigators from academia and industry gathered on April 4 and 5, 2013, in Washington DC at the Arrowhead’s 2nd Annual Cancer Immunotherapy Conference. Two complementary concepts were discussed: cancer “stem cells” as targets and therapeutic platforms based on stem cells.

  17. INTRAPLEURAL IMMUNOTHERAPY FOR METASTATIC PLEURISIES IN PATIENTS WITH BREAST CANCER

    OpenAIRE

    K. S. Titov; L. V. Demidov; M. V. Kiselevsky; I. N. Mikhailova; I. Zh. Shubina; A. N. Gritsai; I. E. Sinelnikov; L. M. Rodionova

    2009-01-01

    Intrapleural immunotherapy for metastatic pleurisies demonstrates a high efficiency in the treatment of patients with breast cancer (BC). This immunotherapy modality is regarded as one of the stages of complex treatment in patients with disseminated BC and allows its capabilities to be extended for their further management.

  18. 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.

  19. Immunotherapy and Immune Evasion in Prostate Cancer

    International Nuclear Information System (INIS)

    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

  20. Mechanisms of allergen-specific immunotherapy

    OpenAIRE

    Fujita Hiroyuki; Soyka Michael B; Akdis Mübeccel; Akdis Cezmi A

    2012-01-01

    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 ro...

  1. Immunotherapy with GD2 specific monoclonal antibodies

    International Nuclear Information System (INIS)

    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 GD2 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

  2. Requirements Elicitation Problems: A Literature Analysis

    Directory of Open Access Journals (Sweden)

    Bill Davey

    2015-06-01

    Full Text Available Requirements elicitation is the process through which analysts determine the software requirements of stakeholders. Requirements elicitation is seldom well done, and an inaccurate or incomplete understanding of user requirements has led to the downfall of many software projects. This paper proposes a classification of problem types that occur in requirements elicitation. The classification has been derived from a literature analysis. Papers reporting on techniques for improving requirements elicitation practice were examined for the problem the technique was designed to address. In each classification the most recent or prominent techniques for ameliorating the problems are presented. The classification allows the requirements engineer to be sensitive to problems as they arise and the educator to structure delivery of requirements elicitation training.

  3. Immunotherapy of Cancer: Towards a New Era

    Directory of Open Access Journals (Sweden)

    John B.A.G. Haanen

    2014-11-01

    Full Text Available In the past two decades, immunotherapy of cancer has developed into an established treatment option. At first, the development of monoclonal antibodies – targeting overexpressed cell surface molecules on tumour cells – resulted in improved survival when combined with standard chemotherapy or radiotherapy. More recently, T cell immunotherapy has impacted on survival of certain cancer types. In melanoma especially, but now also in renal cell cancer and non-small cell lung cancer, immune checkpoint inhibitors, such as cytotoxic T lymphocyte–associated antigen-4 (anti-CTLA4 and blockade of programmed death receptor-1-PD- ligand 1 (PD1-PD-L1 interaction, represent a completely new treatment paradigm, lowering the threshold for an anticancer immune response and breaking self-tolerance. Adoptive T cell transfer using tumour- infiltrating lymphocytes or genetically modified T cells are under development, but have shown impressive clinical efficacy in several Phase II studies. These emerging but highly promising treatments can give rise to durable tumour control in diseases that were lethal in all patients only a few years ago.

  4. A stochastic model for immunotherapy of cancer.

    Science.gov (United States)

    Baar, Martina; Coquille, Loren; Mayer, Hannah; Hölzel, Michael; Rogava, Meri; Tüting, Thomas; Bovier, Anton

    2016-01-01

    We propose an extension of a standard stochastic individual-based model in population dynamics which broadens the range of biological applications. Our primary motivation is modelling of immunotherapy of malignant tumours. In this context the different actors, T-cells, cytokines or cancer cells, are modelled as single particles (individuals) in the stochastic system. The main expansions of the model are distinguishing cancer cells by phenotype and genotype, including environment-dependent phenotypic plasticity that does not affect the genotype, taking into account the effects of therapy and introducing a competition term which lowers the reproduction rate of an individual in addition to the usual term that increases its death rate. We illustrate the new setup by using it to model various phenomena arising in immunotherapy. Our aim is twofold: on the one hand, we show that the interplay of genetic mutations and phenotypic switches on different timescales as well as the occurrence of metastability phenomena raise new mathematical challenges. On the other hand, we argue why understanding purely stochastic events (which cannot be obtained with deterministic models) may help to understand the resistance of tumours to therapeutic approaches and may have non-trivial consequences on tumour treatment protocols. This is supported through numerical simulations. PMID:27063839

  5. Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

    Directory of Open Access Journals (Sweden)

    Bainan Liu

    2013-01-01

    Full Text Available Warm autoimmune hemolytic anemia (WAIHA is one of four clinical types of autoimmune hemolytic anemia (AIHA, with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies.

  6. Personalized cancer immunotherapy using Systems Medicine approaches.

    Science.gov (United States)

    Gupta, Shailendra K; Jaitly, Tanushree; Schmitz, Ulf; Schuler, Gerold; Wolkenhauer, Olaf; Vera, Julio

    2016-05-01

    The immune system is by definition multi-scale because it involves biochemical networks that regulate cell fates across cell boundaries, but also because immune cells communicate with each other by direct contact or through the secretion of local or systemic signals. Furthermore, tumor and immune cells communicate, and this interaction is affected by the tumor microenvironment. Altogether, the tumor-immunity interaction is a complex multi-scale biological system whose analysis requires a systemic view to succeed in developing efficient immunotherapies for cancer and immune-related diseases. In this review we discuss the necessity and the structure of a systems medicine approach for the design of anticancer immunotherapies. We support the idea that the approach must be a combination of algorithms and methods from bioinformatics and patient-data-driven mathematical models conceived to investigate the role of clinical interventions in the tumor-immunity interaction. For each step of the integrative approach proposed, we review the advancement with respect to the computational tools and methods available, but also successful case studies. We particularized our idea for the case of identifying novel tumor-associated antigens and therapeutic targets by integration of patient's immune and tumor profiling in case of aggressive melanoma. PMID:26174229

  7. Immunological mechanisms of allergen-specific immunotherapy.

    Science.gov (United States)

    Jutel, Marek; Akdis, C A

    2011-06-01

    The studies on the mechanisms of specific immunotherapy (SIT) point out its targets that decide on the efficacy of SIT and hence might be used for its further improvement. Several mechanisms have been proposed to explain the beneficial effects of immunotherapy. The knowledge of the mechanisms underlying allergic diseases and curative treatment possibilities has experienced exciting advances over the last three decades. Studies in several clinical trials in allergen-SIT have demonstrated that the induction of a tolerant state against allergens in many ways represents a key step in the development of a healthy immune response against allergens. Several cellular and molecular mechanisms have been demonstrated: allergen-specific suppressive capacities of both inducible subsets of CD4(+) CD25(+) forkhead box P3(+) T-regulatory and IL-10-secreting type 1 T-regulatory cells increase in peripheral blood; suppression of eosinophils, mast cells, and basophils; Ab isotype change from IgE to IgG4. This review aims at the better understanding of the observed immunological changes associated with allergen SIT. PMID:21466562

  8. Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies.

    Science.gov (United States)

    Gastaldi, Matteo; Thouin, Anaïs; Vincent, Angela

    2016-01-01

    Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins. Most importantly, the new antibody-associated diseases almost invariably respond to immunotherapies with considerable and sometimes complete recovery, and there is convincing evidence of their pathogenicity in the relatively limited studies performed so far. Treatments include first-line steroids, intravenous immunoglobulins, and plasma exchange, and second-line rituximab and cyclophosphamide, followed in many cases by steroid-sparing agents in the long-term. This review focuses mainly on N-methyl D-aspartate receptor- and voltage-gated potassium channel complex-related Abs in adults, the clinical phenotypes, and treatment responses. Pediatric cases are referred to but not reviewed in detail. As there have been very few prospective studies, the conclusions regarding immunotherapies are based on retrospective studies. PMID:26692392

  9. Peptide immunotherapy in experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Stephen M Anderton

    2015-06-01

    Full Text Available We now have potent drugs available to treat the inflammatory component of multiple sclerosis (MS. However, not all patients respond, the drugs are not curative, and the associated risks to beneficial immune surveillance are considerable. A more desirable approach is to specifically target those comparatively rare T lymphocytes that are orchestrating the autoimmune attack. Using the autoantigen itself to instill immune tolerance in those cells remains a holy grail of immunotherapy. Peptide immunotherapy (PIT is highly effective at silencing autoimmune responses in experimental autoimmune encephalomyelitis (EAE, and clinical trials of PIT are underway in MS. This review discusses the current paradigms for PIT-induced tolerance in naïve T cells. It highlights the need for better understanding of the mode of action of PIT upon memory and effector T cells that are responsible for driving/sustaining ongoing autoimmune pathology. Recent studies in EAEsuggest genetic and epigenetic changes in these pathogenic T-cell populations in response to PIT. Finally, future challenges to effective translation of PIT to the clinic are considered.

  10. 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, with the...

  11. Evolving synergistic combinations of targeted immunotherapies to combat cancer.

    Science.gov (United States)

    Melero, Ignacio; Berman, David M; Aznar, M Angela; Korman, Alan J; Pérez Gracia, José Luis; Haanen, John

    2015-08-01

    Immunotherapy has now been clinically validated as an effective treatment for many cancers. There is tremendous potential for synergistic combinations of immunotherapy agents and for combining immunotherapy agents with conventional cancer treatments. Clinical trials combining blockade of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) may serve as a paradigm to guide future approaches to immuno-oncology combination therapy. In this Review, we discuss progress in the synergistic design of immune-targeting combination therapies and highlight the challenges involved in tailoring such strategies to provide maximal benefit to patients. PMID:26205340

  12. Improving cancer immunotherapy by targeting the STATe of MDSCs

    Science.gov (United States)

    de Haas, Nienke; de Koning, Coco; Spilgies, Lisanne; de Vries, I. Jolanda M.; Hato, Stanleyson V.

    2016-01-01

    ABSTRACT Cancer immunotherapy is a promising therapeutic avenue; however, in practice its efficacy is hampered by an immunosuppressive tumor microenvironment that consists of suppressive cell types like myeloid-derived suppressor cells (MDSCs). Eradication or reprogramming of MDSCs could therefore enhance clinical responses to immunotherapy. Here, we review clinically available drugs that target MDSCs, often through inhibition of STAT signaling, which is essential for MDSC accumulation and suppressive functions. Interestingly, several drugs used for non-cancerous indications and natural compounds similarly inhibit MDSCs by STAT inhibition, but have fewer side effects than anticancer drugs. Therefore, they show great potential for combination strategies with immunotherapy.

  13. Workshop on immunotherapy combinations. Society for immunotherapy of cancer annual meeting Bethesda, November 3, 2011

    OpenAIRE

    Forero Ivan; Okada Hideho; Topalian Suzanne L; Gajewski Thomas F; Korman Alan J; Melero Ignacio

    2012-01-01

    Abstract Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination imm...

  14. Requirement Elicitation for Requirement in Software Engineering

    OpenAIRE

    Swathine.K*; Dr. J.KomalaLakshmi

    2014-01-01

    Requirement Elicitation is also called as Requirement Gathering, in which requirements are collected from User, Stakeholders, and Customer to build the system. Requirements elicitation practices include interviews, questionnaires, task analysis, domain analysis, user observation, workshops, brainstorming, use cases, role playing and prototyping by using this practices quality of the requirements are satisfied. A wide variety of tools exist that have been developed and used to supp...

  15. Novel targets for immunotherapy in glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Mary H Foster

    2008-09-01

    Full Text Available Mary H FosterDepartment of Medicine and Research Service, Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham, North Carolina, USAAbstract: Glomerulonephritis is a common cause of chronic kidney disease and end stage renal failure. Current therapy relies on variably effective, nonspecific and toxic immunosuppression. Recent insights into underlying biology and disease pathogenesis in human glomerulonephritis combined with advances in the fields of inflammation and autoimmunity promise a cadre of novel targeted interventions. This review highlights the therapeutic potential of two antigens, alpha3 (IVNC1 collagen and podocyte neutral endopeptidase, and two cell signaling and effector molecules, IgG Fc receptors and complement, judged to be particularly amenable to therapeutic manipulation in man. It is anticipated that continued dissection of pathogenesis in the diverse disorders that comprise the glomerulonephritides will provide the basis for individualized disease-specific therapy.Keywords: glomerulonephritis, immunotherapy, Goodpasture syndrome, membranous nephropathy

  16. Biomarkers for Allergen Immunotherapy: A "Panoromic" View.

    Science.gov (United States)

    Moingeon, Philippe

    2016-02-01

    Biomarkers (BMKs) are biological parameters that can be measured to predict or monitor disease severity or treatment efficacy. The induction of regulatory dendritic cells (DCs) concomitantly with a downregulation of proallergic DC2s (ie, DCs supporting the differentiation of T-helper lymphocyte type 2 cells) in the blood of patients allergic to grass pollen has been correlated with the early onset of allergen immunotherapy efficacy. The combined use of omics technologies to compare biological samples from clinical responders and nonresponders is being implemented in the context of nonhypothesis-driven approaches. Such comprehensive "panoromic" strategies help identify completely novel candidate BMKs, to be subsequently validated as companion diagnostics in large-scale clinical trials. PMID:26617233

  17. 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.

  18. Immunotherapy of hematological malignancies using dendritic cells.

    Science.gov (United States)

    Van de Velde, Ann L R; Berneman, Zwi N; Van Tendeloo, Viggo F I

    2008-03-01

    The arsenal of therapeutic weapons against hematological malignancies is constantly growing. Unravelling the secrets of tumor immunobiology has allowed researchers to manipulate the immune system in order to stimulate tumor immunity or to bypass tumor-induced immunosuppression. An area of great interest is active specific immunotherapy where dendritic cell (DC)-based therapeutic vaccines for cancer have definitely grabbed the spotlight. DC are intensively investigated as cellular adjuvants to harness the immune system to fight off cancer by augmenting the number and effector functions of tumor-specific CD8+ cytotoxic T lymphocytes. In the present review we present a comprehensive synopsis and an update of the use of DC in hematological malignancies. In the future, more basic research as well as more clinical trials are warranted to fully establish the value of DC vaccination as an adjuvant therapy for modern hematological oncology. PMID:18390412

  19. Sublingual immunotherapy in the treatment of children.

    Science.gov (United States)

    Pham-Thi, N; de Blic, J; Scheinmann, P

    2006-01-01

    Children with controlled intermittent mild-to-moderate asthma, controlled rhinitis and a single sensitivity may be appropriate candidates for sublingual immunotherapy (SLIT). Positive effects of SLIT may depend on initiation in early childhood and a long duration of treatment. To ensure optimum compliance, sociological, economic and familial factors should also be taken in to consideration when prescribing SLIT. Evidence from recent long-term trials indicates that SLIT interfered with the atopic march and the allergic progression from rhinitis to asthma without any severe adverse side effects. Local immune response has been seen to be blunted with SLIT, which suggests that treatment has an immunomodulatory effect. In addition, it may also decrease the risk of new sensitizations. Ongoing developments in SLIT, particularly advances in dosing and new indications, such as food allergies, will increase the use of this treatment modality in children. PMID:16792599

  20. Immune checkpoint‑targeted cancer immunotherapies

    Directory of Open Access Journals (Sweden)

    Julian Swatler

    2016-01-01

    Full Text Available Tumor cells may express on their surface various characteristic antigens that can induce antitumor immunity. However, cancer in human body may induce an immunosuppressive microenvironment that limits immune response to its antigens. For many years scientists have tried to develop an immunotherapy which would induce a potent antitumor immune response and lead to an elimination of the disease. One of the most promising immunotherapies is blockade of immune checkpoints, i.e. a group of costimulatory molecules negatively regulating the immune system. Their blockade would overcome immune tolerance in the tumor microenvironment and amplify antitumor immunity. What’s more, immune checkpoint blockade may turn out even more profitable, as some of immune checkpoints and their ligands are expressed on tumor surface and on tumor infiltrating lymphocytes, contributing to the immunosuppressive cancer microenvironment. Phase III clinical trials have confirmed efficacy of an anti‑CTLA‑4 antibody ipilimumab, thereby leading to its acceptance for the treatment of advanced melanoma. Thanks to promising results of the phase I clinical trials, a breakthrough therapy designation and an early approval for the treatment have been granted to anti‑PD‑1 antibodies ‑ nivolumab (for the treatment of advanced melanoma and advanced non‑small cell lung cancer and pembrolizumab (for the treatment of advanced melanoma and, in the treatment of advanced bladder cancer, an anti‑PD‑L1 antibody ‑ MPDL3280A as well. Other immune checkpoints, such as LAG‑3, TIM‑3, BTLA, B7‑H3 and B7‑H4, are also under early evaluation.

  1. 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.

  2. A practical view of immunotherapy for food allergy

    OpenAIRE

    Song, Tae Won

    2016-01-01

    Food allergy is common and sometimes life threatening for Korean children. The current standard treatment of allergen avoidance and self-injectable epinephrine does not change the natural course of food allergy. Recently, oral, sublingual, and epicutaneous immunotherapies have been studied for their effectiveness against food allergy. While various rates of desensitization (36% to 100%) and tolerance (28% to 75%) have been induced by immunotherapies for food allergy, no single established pro...

  3. Cancer immunotherapy: the beginning of the end of cancer?

    OpenAIRE

    Farkona, Sofia; Diamandis, Eleftherios P.; Blasutig, Ivan M

    2016-01-01

    These are exciting times for cancer immunotherapy. After many years of disappointing results, the tide has finally changed and immunotherapy has become a clinically validated treatment for many cancers. Immunotherapeutic strategies include cancer vaccines, oncolytic viruses, adoptive transfer of ex vivo activated T and natural killer cells, and administration of antibodies or recombinant proteins that either costimulate cells or block the so-called immune checkpoint pathways. The recent succe...

  4. Dendritic cell-based cancer immunotherapy for colorectal cancer

    OpenAIRE

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are curr...

  5. Regulation of cell death in cancer - possible implications for immunotherapy

    OpenAIRE

    Simone eFulda

    2013-01-01

    Since most anticancer therapies including immunotherapy trigger programmed cell death in cancer cells, defective cell death programs can lead to treatment resistance and tumor immune escape. Therefore, evasion of programmed cell death may provide one possible explanation as to why cancer immunotherapy has so far only shown modest clinical benefits for children with cancer. A better understanding of the molecular mechanisms that regulate sensitivity and resistance to programmed cell death is e...

  6. Thyroid dysfunction associated with immunotherapy for patients with cancer.

    Science.gov (United States)

    Schwartzentruber, D J; White, D E; Zweig, M H; Weintraub, B D; Rosenberg, S A

    1991-12-01

    The authors performed a prospective study to evaluate thyroid dysfunction in 130 patients with cancer who were receiving interleukin-2 (IL-2)-based immunotherapy. Primary hypothyroidism was the most common abnormality, occurring in 12% of patients before, 38% during, and 23% after immunotherapy. Hyperthyroidism occurred in 1%, 4%, and 7% of patients at those time intervals. Among patients initially euthyroid (n = 111), primary hypothyroidism developed in 32% during and 14% after immunotherapy, persisting a median of 54 days. Three patients required levothyroxine. Hyperthyroidism developed in 2% of patients during immunotherapy and 6% after. Thyroid dysfunction was not a function of sex, diagnosis, type of treatment, or response to immunotherapy. Elevated titers of antithyroglobulin and antithyroid microsomal antibodies were detected after treatment in 9% and 7%, respectively, of all patients without prior antibody abnormalities and did not correlate with response to therapy. The high incidence of therapy-induced thyroid dysfunction suggests that thyroid function should be carefully monitored in all patients receiving IL-2-based immunotherapy. PMID:1933775

  7. Stereoscopy Amplifies Emotions Elicited by Facial Expressions.

    Science.gov (United States)

    Hakala, Jussi; Kätsyri, Jari; Häkkinen, Jukka

    2015-12-01

    Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately) and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants' gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm) camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15-65 mm) base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions. PMID:27551358

  8. Rational elicitation of cold-sensitive phenotypes.

    Science.gov (United States)

    Baliga, Chetana; Majhi, Sandipan; Mondal, Kajari; Bhattacharjee, Antara; VijayRaghavan, K; Varadarajan, Raghavan

    2016-05-01

    Cold-sensitive phenotypes have helped us understand macromolecular assembly and biological phenomena, yet few attempts have been made to understand the basis of cold sensitivity or to elicit it by design. We report a method for rational design of cold-sensitive phenotypes. The method involves generation of partial loss-of-function mutants, at either buried or functional sites, coupled with selective overexpression strategies. The only essential input is amino acid sequence, although available structural information can be used as well. The method has been used to elicit cold-sensitive mutants of a variety of proteins, both monomeric and dimeric, and in multiple organisms, namely Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster This simple, yet effective technique of inducing cold sensitivity eliminates the need for complex mutations and provides a plausible molecular mechanism for eliciting cold-sensitive phenotypes. PMID:27091994

  9. Doxil Synergizes with Cancer Immunotherapies to Enhance Antitumor Responses in Syngeneic Mouse Models

    Directory of Open Access Journals (Sweden)

    Jonathan Rios-Doria

    2015-08-01

    Full Text Available Based on the previously described roles of doxorubicin in immunogenic cell death, both doxorubicin and liposomal doxorubicin (Doxil were evaluated for their ability to boost the antitumor response of different cancer immunotherapies including checkpoint blockers (anti–PD-L1, PD-1, and CTLA-4 mAbs and TNF receptor agonists (OX40 and GITR ligand fusion proteins in syngeneic mouse models. In a preventative CT26 mouse tumor model, both doxorubicin and Doxil synergized with anti–PD-1 and CTLA-4 mAbs. Doxil was active when CT26 tumors were grown in immunocompetent mice but not immunocompromised mice, demonstrating that Doxil activity is increased in the presence of a functional immune system. Using established tumors and maximally efficacious doses of Doxil and cancer immunotherapies in either CT26 or MCA205 tumor models, combination groups produced strong synergistic antitumor effects, a larger percentage of complete responders, and increased survival. In vivo pharmacodynamic studies showed that Doxil treatment decreased the percentage of tumor-infiltrating regulatory T cells and, in combination with anti–PD-L1, increased the percentage of tumor-infiltrating CD8+ T cells. In the tumor, Doxil administration increased CD80 expression on mature dendritic cells. CD80 expression was also increased on both monocytic and granulocytic myeloid cells, suggesting that Doxil may induce these tumor-infiltrating cells to elicit a costimulatory phenotype capable of activating an antitumor T-cell response. These results uncover a novel role for Doxil in immunomodulation and support the use of Doxil in combination with checkpoint blockade or TNFR agonists to increase response rates and antitumor activity.

  10. Chapter 3: Allergen immunotherapy: definition, indication, and reactions.

    Science.gov (United States)

    Georgy, Mary S; Saltoun, Carol A

    2012-01-01

    Specific allergen immunotherapy is the administration of increasing amounts of specific allergens to which the patient has type I immediate hypersensitivity. It is a disease modifying therapy, indicated for the treatment of allergic rhinitis, allergic asthma, and hymenoptera hypersensitivity. Specific IgE antibodies for appropriate allergens for immunotherapy must be documented. Indications for allergen immunotherapy include (1) inadequate symptom control despite pharmacotherapy and avoidance measures, (2) a desire to reduce the morbidity from allergic rhinitis and/or asthma or reduce the risk of anaphylaxis from a future insect sting, (3) when the patient experiences undesirable side effects from pharmacotherapy, and (4) when avoidance is not possible. Furthermore, patients may seek to benefit from economic savings of allergen immunotherapy compared with pharmacotherapy over time. Several studies have reported that immunotherapy in children with allergic rhinitis appears to prevent the development of new allergic sensitizations and/or new-onset asthma. Humoral, cellular, and tissue level changes occur with allergen immunotherapy including large increases in antiallergen IgG(4) antibodies, a decrease in the postseasonal rise of antiallergen IgE antibodies, reduced numbers of nasal mucosal mast cells and eosinophils, induction of Treg cells, and suppression of Th2 more than Th1 lymphocytes. There is a corresponding increase in IL-10 and transforming growth factor beta. In the United States, allergen immunotherapy is administered by the subcutaneous route in the physician's office, whereas primarily in some countries in Europe, it is administered for allergic rhinitis and asthma by the sublingual route by the patient at home. PMID:22794676

  11. Eliciting Subjective Probabilities with Binary Lotteries

    DEFF Research Database (Denmark)

    Harrison, Glenn W.; Martínez-Correa, Jimmy; Swarthout, J. Todd

    2014-01-01

    We evaluate a binary lottery procedure for inducing risk neutral behavior in a subjective belief elicitation task. Prior research has shown this procedure to robustly induce risk neutrality when subjects are given a single risk task defined over objective probabilities. Drawing a sample from the...... same subject population, we find evidence that the binary lottery procedure also induces linear utility in a subjective probability elicitation task using the Quadratic Scoring Rule. We also show that the binary lottery procedure can induce direct revelation of subjective probabilities in subjects with...

  12. A Discussion of Usefulness and Pitfall of Elicitation and Introspection

    Institute of Scientific and Technical Information of China (English)

    陈燕娜

    2013-01-01

    Nowadays, many scholars would like to use evidence derived from elicitation and introspection in their research. Both elicitation and introspection are common methods of data collection. The essay discusses the usefulness and pitfall of elicitation and introspection. It finds out that both elicitation and introspection have their own advantages and disadvantages.

  13. Effects of laser immunotherapy on tumor microenvironment

    Science.gov (United States)

    Acquaviva, Joseph T.; Wood, Ethan W.; Hasanjee, Aamr; Chen, Wei R.; Vaughan, Melville B.

    2014-02-01

    The microenvironments of tumors are involved in a complex and reciprocal dialog with surrounding cancer cells. Any novel treatment must consider the impact of the therapy on the microenvironment. Recently, clinical trials with laser immunotherapy (LIT) have proven to effectively treat patients with late-stage, metastatic breast cancer and melanoma. LIT is the synergistic combination of phototherapy (laser irradiation) and immunological stimulation. One prominent cell type found in the tumor stroma is the fibroblast. Fibroblast cells can secrete different growth factors and extracellular matrix modifying molecules. Furthermore, fibroblast cells found in the tumor stroma often express alpha smooth muscle actin. These particular fibroblasts are coined cancer-associated fibroblast cells (CAFs). CAFs are known to facilitate the malignant progression of tumors. A collagen lattice assay with human fibroblast cells is used to elucidate the effects LIT has on the microenvironment of tumors. Changes in the contraction of the lattice, the differentiation of the fibroblast cells, as well as the proliferation of the fibroblast cells will be determined.

  14. Aptamers: A Feasible Technology in Cancer Immunotherapy

    Science.gov (United States)

    Villanueva, H.; Pastor, F.

    2016-01-01

    Aptamers are single-chained RNA or DNA oligonucleotides (ODNs) with three-dimensional folding structures which allow them to bind to their targets with high specificity. Aptamers normally show affinities comparable to or higher than that of antibodies. They are chemically synthesized and therefore less expensive to manufacture and produce. A variety of aptamers described to date have been shown to be reliable in modulating immune responses against cancer by either blocking or activating immune receptors. Some of them have been conjugated to other molecules to target the immune system and reduce off-target side effects. Despite the success of first-line treatments against cancer, the elevated number of relapsing cases and the tremendous side effects shown by the commonly used agents hinder conventional treatments against cancer. The advantages provided by aptamers could enhance the therapeutic index of a given strategy and therefore enhance the antitumor effect. Here we recapitulate the provided benefits of aptamers with immunomodulatory activity described to date in cancer therapy and the benefits that aptamer-based immunotherapy could provide either alone or combined with first-line treatments in cancer therapy. PMID:27413756

  15. Driving an improved CAR for cancer immunotherapy.

    Science.gov (United States)

    Huang, Xiaopei; Yang, Yiping

    2016-08-01

    The recent clinical success of chimeric antigen receptor (CAR) T cell therapy for B cell malignancies represents a paradigm shift in cancer immunotherapy. Unfortunately, application of CAR T cell-mediated therapy for solid tumors has so far been disappointing, and the reasons for this poor response in solid tumors remain unknown. In this issue of the JCI, Cherkassky and colleagues report on their use of a murine model of human pleural mesothelioma to explore potential factors that limit CAR T cell efficacy. Their studies have uncovered the importance of the tumor microenvironment in the inhibition of CAR T cell functions, revealed a critical role for the programmed death-1 (PD-1) pathway in CAR T cell exhaustion within the tumor microenvironment, and demonstrated improved antitumor effects with a CAR T cell-intrinsic PD-1 blockade strategy using a dominant negative form of PD-1. Together, the results of this study lay the groundwork for further evaluation of mechanisms underlying CAR T cell immune evasion within the tumor microenvironment for the improvement of CAR T cell-mediated therapy for solid tumors. PMID:27454296

  16. Advances in cancer immunology and cancer immunotherapy.

    Science.gov (United States)

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models. PMID:27011048

  17. 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

  18. Mechanisms of allergen-specific immunotherapy.

    Science.gov (United States)

    Fujita, Hiroyuki; Soyka, Michael B; Akdis, Mübeccel; Akdis, Cezmi A

    2012-01-01

    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. PMID:22409879

  19. 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.

  20. Allergen Immunotherapy: Past, Present, and Future.

    Science.gov (United States)

    Jutel, Marek; Kosowska, Anna; Smolinska, Sylwia

    2016-05-01

    Allergen-specific immunotherapy (AIT), although in clinical use for more than a century, is still the only causal treatment of allergic diseases. The safety and efficacy of AIT has been demonstrated in a large number of clinical trials. In addition to allergy symptom reduction AIT plays an essential role in preventing new allergies and asthma and shows long-term effects after discontinuation of treatment. Ideally, it is capable of curing allergy. However, AIT is not effective in all allergic individuals and is not equally effective in the treatment of various hypersensitivities to different allergens. For many years, the route of administration and the vaccine compositions have been evolving. Still there is a strong need for research in the field of new AIT modalities to increase its effectiveness and safety. Growing evidence on immunological effects of AIT, especially new T cell subsets involved in antigen/allergen tolerance, provides novel concepts for safer and more effective vaccination. Pharmacoeconomic studies have demonstrated a clear advantage of AIT over pharmacologic therapies. PMID:26922928

  1. 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.

  2. Changes in Peak Flow Value during Immunotherapy Administration

    International Nuclear Information System (INIS)

    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

  3. Immunotherapy in colorectal cancer: What have we learned so far?

    Science.gov (United States)

    Sanchez-Castañón, María; Er, Tze-Kiong; Bujanda, Luis; Herreros-Villanueva, Marta

    2016-09-01

    After decades of progress based on chemotherapy and targeted agents, patients with metastatic colorectal cancer still have low long-term survival, with more than 500,000 deaths occurring worldwide every year. Recent results showing clinical evidence of efficacy using immunotherapy in other types of tumors, such as melanoma and lung cancer, have also made this a viable therapy for evaluation in colorectal cancer in clinical trials. The development of cancer immunotherapies is progressing quickly, with a variety of technological approaches. This review summarizes the current status of clinical trials testing immunotherapy in colorectal cancer and discusses what has been learned based on previous results. Immunotherapy strategies, such as various models of vaccines, effector-cell therapy and checkpoint inhibitor antibodies, provide protection against progression for a limited subset of patients diagnosed with colorectal cancer. A better understanding of particular immune cell types and pathways in each patient is still needed. These findings will enable the development of novel biomarkers to select the appropriate subset of patients to be treated with a particular immunotherapy, and the tendencies determined from recent results can guide clinical practice for oncologists in this new therapeutic area and in the design of the next round of clinical trials. PMID:27350293

  4. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    Directory of Open Access Journals (Sweden)

    Brian J. Ahn

    2013-11-01

    Full Text Available 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.

  5. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    International Nuclear Information System (INIS)

    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

  6. Eliciting Subjective Probabilities with Binary Lotteries

    DEFF Research Database (Denmark)

    Harrison, Glenn W.; Martínez-Correa, Jimmy; Swarthout, J. Todd

    We evaluate the binary lottery procedure for inducing risk neutral behavior in a subjective belief elicitation task. Harrison, Martínez-Correa and Swarthout [2013] found that the binary lottery procedure works robustly to induce risk neutrality when subjects are given one risk task defined over o...

  7. Affective multimodal mirror: sensing and eliciting laughter

    NARCIS (Netherlands)

    Melder, W.A.; Truong, K.P.; Uyl, M. den; Leeuwen, D.A. van; Neerincx, M.A.; Loos, L.R.; Stock Plum, B.

    2007-01-01

    In this paper, we present a multimodal affective mirror that senses and elicits laughter. Currently, the mirror contains a vocal and a facial affect-sensing module, a component that fuses the output of these two modules to achieve a user-state assessment, a user state transition model, and a compone

  8. Pathological Mobilization and Activities of Dendritic Cells in Tumor-Bearing Hosts: Challenges and Opportunities for Immunotherapy of Cancer

    Science.gov (United States)

    Tesone, Amelia J.; Svoronos, Nikolaos; Allegrezza, Michael J.; Conejo-Garcia, Jose R.

    2013-01-01

    A common characteristic of solid tumors is the pathological recruitment of immunosuppressive myeloid cells, which in certain tumors includes dendritic cells (DCs). DCs are of particular interest in the field of cancer immunotherapy because they induce potent and highly specific anti-tumor immune responses, particularly in the early phase of tumorigenesis. However, as tumors progress, these cells can be transformed into regulatory cells that contribute to an immunosuppressive microenvironment favoring tumor growth. Therefore, controlling DC phenotype has the potential to elicit effective anti-tumor responses while simultaneously weakening the tumor’s ability to protect itself from immune attack. This review focuses on the dual nature of DCs in the tumor microenvironment, the regulation of DC phenotype, and the prospect of modifying DCs in situ as a novel immunotherapeutic approach. PMID:24339824

  9. The efficiency of peptide immunotherapy for respiratory allergy.

    Science.gov (United States)

    Incorvaia, Cristoforo; Montagni, Marcello; Ridolo, Erminia

    2016-06-01

    Allergen immunotherapy (AIT) was introduced more than a century ago and is yet the only disease-modifying treatment for allergy. AIT is currently conducted with whole allergen extracts and several studies clearly support its efficacy in the treatment of respiratory allergies, however the need for a long treatment - that affects costs and patients compliance - and possible IgE-mediated adverse events are still unresolved issues. Peptide immunotherapy is based on the use of short synthetic peptides which represent major T-cell epitopes of the allergen with markedly reduced ability to cross-link IgE and activate mast cells and basophils. Data from clinical trials confirmed the efficacy and tolerability of peptide immunotherapy in patients with cat allergy, with a sustained clinical effect after a short course treatment. Peptide therapy is a promising safe and effective new specific treatment for allergy to be developed for the most important allergens causing rhinitis or asthma. PMID:26901667

  10. Advances in Immunotherapies for Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuan HE

    2014-03-01

    Full Text Available Globally, Lung cancer is the leading cause of cancer-related death of high morbidity and mortality with poor prognosis, which needs some more effective and less toxic therapies. The immunotherapies offer a novel approach for the treatment of patients with non-small cell lung cancer (NSCLC in both the adjuvant and palliative disease settings. A number of promising immunotherapies based on different mechanism have now been evaluated showing an increasing response rate. Moreover, further phase II/III clinical trials will be indicated to explore its value. These include checkpoint inhibitors (anti-CTLA4 antibody, anti-PD-1 antibody, anti-PD-L1 antibody, active vaccination (L-BLP25 liposome vaccine, Belagenpumatucel-L vaccine, MAGE-A3 protein vaccine and adoptive vaccination (CIK cells. The purpose of this paper will draw a summary on the theory, clinical trials, toxicity and problems to be solved of the immunotherapies in NSCLC.

  11. Treating allergic rhinitis by sublingual immunotherapy: a review

    Directory of Open Access Journals (Sweden)

    Cristoforo Incorvaia

    2012-06-01

    Full Text Available OBJECTIVE: Allergic rhinitis (AR is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT, but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years.

  12. Immunotherapy in human colorectal cancer: Challenges and prospective.

    Science.gov (United States)

    Sun, Xuan; Suo, Jian; Yan, Jun

    2016-07-28

    Human colorectal cancer (CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC. In this review, we will discuss important immunological landscape within the CRC microenvironment and introduce immunoscore system to better describe immunophenotyping in CRC. We will also discuss different immunotherapeutic approaches currently utilized in different phases of clinical trials. Some of those completed or ongoing trials are summarized. Finally, we provide a brief prospective on the future human CRC immunotherapy. PMID:27605872

  13. 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.

  14. The Role of Surgical Pathology in Guiding Cancer Immunotherapy.

    Science.gov (United States)

    Lovitch, Scott B; Rodig, Scott J

    2016-05-23

    The recognition that the immune system can identify and destroy tumor cells has driven a paradigm shift in our understanding of human cancer. Therapies designed to enhance this capacity, including cancer vaccines and coinhibitory receptor blockade, have demonstrated clinical efficacy in treating tumors refractory to conventional therapy. In this review, we discuss how the analysis of the immune microenvironment in primary tissue biopsy samples can be used to stratify patients according to clinical outcome, identify patients likely to benefit from specific immunotherapies, and tailor combination immunotherapy to individual patients and tumor types. As immunotherapy gains in complexity and is used in combination with agents that target oncogenic, intracellular signaling pathways, diagnostic pathologists will play an increasingly important part in identifying and quantifying cellular and molecular biomarkers in tissue samples that reflect the nature and magnitude of the antitumor immune response. PMID:27193453

  15. Immunotherapy for Urothelial Carcinoma: Current Status and Perspectives

    International Nuclear Information System (INIS)

    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

  16. Limbic encephalitis following immunotherapy against metastatic malignant melanoma.

    Science.gov (United States)

    Salam, Sharfaraz; Lavin, Timothy; Turan, Ayse

    2016-01-01

    Novel immunotherapies are increasingly being used to treat malignant melanoma. The use of such agents has been associated with triggering autoimmunity. However, there has been a paucity in reports of limbic encephalitis associated with these immunotherapies. Pembrolizumab, a monoclonal antibody against programmed cell death antigen (PD-1), is currently being trialled in the UK to treat malignant melanoma. We report a unique case of antibody-negative limbic encephalitis presenting 1 year after starting pembrolizumab, in the context of malignant melanoma. The patient presented with progressive cognitive decline. MRI of the brain revealed signal change within the limbic structures. Cerebrospinal fluid studies confirmed evidence of inflammation with raised white cell count and protein. We were able to prevent further progression of symptoms by stopping pembrolizumab and treating the patient instead with steroids. We advocate considering autoimmune neuroinflammation as a differential for neurological disorders presenting in patients receiving PD-1 antagonist treatment and immunotherapy in general. PMID:27009198

  17. 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.

  18. Adapting Cancer Immunotherapy Models for the Real World.

    Science.gov (United States)

    Klevorn, Lauryn E; Teague, Ryan M

    2016-06-01

    Early experiments in mice predicted the success of checkpoint blockade immunotherapy in cancer patients. However, these same animal studies failed to accurately predict many of the limitations and toxicities of treatment. One of the likely reasons for this discrepancy is the nearly universal use of young healthy mice, which stand in stark contrast to diverse patient populations varying in age, weight, diet, and hygiene. Because these variables impact immunity and metabolism, they also influence outcomes during immunotherapy and should be incorporated into the study design of preclinical experiments. Here, we discuss recent findings that highlight how efficacy and toxicity of cancer immunotherapy are affected by patient variation, and how distinct host environments can be better modeled in animal studies. PMID:27105824

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

    International Nuclear Information System (INIS)

    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

  20. Cancer Immunotherapy: Selected Targets and Small-Molecule Modulators.

    Science.gov (United States)

    Weinmann, Hilmar

    2016-03-01

    There is a significant amount of excitement in the scientific community around cancer immunotherapy, as this approach has renewed hope for many cancer patients owing to some recent successes in the clinic. Currently available immuno-oncology therapeutics under clinical development and on the market are mostly biologics (antibodies, proteins, engineered cells, and oncolytic viruses). However, modulation of the immune system with small molecules offers several advantages that may be complementary and potentially synergistic to the use of large biologicals. Therefore, the discovery and development of novel small-molecule modulators is a rapidly growing research area for medicinal chemists working in cancer immunotherapy. This review provides a brief introduction into recent trends related to selected targets and pathways for cancer immunotherapy and their small-molecule pharmacological modulators. PMID:26836578

  1. The acute and sensitization effects of tumor necrosis factor-α: implications for immunotherapy as well as psychiatric and neurological conditions.

    Science.gov (United States)

    Hayley, Shawn; Merali, Zul; Anisman, Hymie

    2002-12-01

    In addition to their role as signaling molecules of the immune system, cytokines may participate in central neurotransmission. Variations of the central and/or peripheral levels of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-β (IL-1β), impact on neuroendocrine processes as well as central neurotransmitter activity. To a considerable extent, these effects are reminiscent of those elicited by psychogenic stressors. The current review describes recent findings consistent with a role for these cytokines in the neurochemical and behavioral manifestations of clinical depression, as well as the cellular death associated with cerebral ischemia. Moreover, the increasing use of cytokines in the immunotherapeutic treatment of various autoimmune diseases (e.g. rheumatoid arthritis) and cancers prompted us to consider the potential role of central processes in subserving the mood-related side-effects elicited by these treatments. Finally, a single administration of TNF-α has been shown to elicit a time-dependent sensitization effect, wherein the behavioral and neurochemical responses elicited by later cytokine treatment are greatly enhanced. Thus, particular attention was devoted to the possibility that elevated levels of TNF-α, through either exogenous (e.g. immunotherapy) or endogenous (e.g. brain damage or stressors) means may sensitize neurotransmitter or second messenger pathways important for the pathology. Given the time-dependent nature of cytokine sensitization effects, the schedule of cytokine administration during immunotherapy, or the timing of cytokine up-regulation in response to traumatic or stressful events may favor the development of sensitized central processes, which may influence clinical outcome. PMID:26984578

  2. A comparison of five elicitation techniques for elicitation of attributes of low involvement products

    DEFF Research Database (Denmark)

    Bech-Larsen, Tino; Nielsen, Niels Asger

    1999-01-01

    dimensions directed from theories of consumer buying behaviour. Although a number of differences between the techniques are identified in the study, the main findings are that the robustness of the different techniques for attribute elicitation is considerable Udgivelsesdato: JUN...

  3. Dendritic cell-based cancer immunotherapy for colorectal cancer

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  4. Novel anti-melanoma treatment:focus on immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Meng-Ze Hao; Wen-Ya Zhou; Xiao-Ling Du; Ke-Xin Chen; Guo-Wen Wang; Yun Yang; Ji-Long Yang

    2014-01-01

    Melanoma is an intractable cancer that is aggressive, lethal, and metastatic. The prognosis of advanced melanoma is very poor because it is insensitive to chemotherapy and radiotherapy. The incidence of melanoma has been ascending stably for years worldwide, accompanied by increasing mortality. New approaches to managing this deadly disease are much anticipated to enhance the cure rate and to extend clinical benefits to patients with metastatic melanoma. Due to its high degree of immunogenicity, melanoma could be a good target for immunotherapy, which has been developed for decades and has achieved certain progress. This article provides an overview of immunotherapy for melanoma.

  5. Novel anti-melanoma treatment: focus on immunotherapy

    Directory of Open Access Journals (Sweden)

    Meng-Ze Hao

    2014-09-01

    Full Text Available Melanoma is an intractable cancer that is aggressive, lethal, and metastatic. The prognosis of advanced melanoma is very poor because it is insensitive to chemotherapy and radiotherapy. The incidence of melanoma has been ascending stably for years worldwide, accompanied by increasing mortality. New approaches to managing this deadly disease are much anticipated to enhance the cure rate and to extend clinical benefits to patients with metastatic melanoma. Due to its high degree of immunogenicity, melanoma could be a good target for immunotherapy, which has been developed for decades and has achieved certain progress. This article provides an overview of immunotherapy for melanoma.

  6. 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....

  7. Can packaging elements elicit consumers’ emotional responses?

    DEFF Research Database (Denmark)

    Liao, Lewis; Corsi, Armando; Lockshin, Larry;

    Emotion has been an important concept in many areas of consumer research such as judgment, decision-making and advertising. Little research has been done on emotion in packaging adopting the physiological measures used in other areas. This paper draws on past studies in advertising that measure...... emotional responses toward image, colour and font, and apply them to packaging research. The study tests the extent at which packaging can elicit consumers’ spontaneous emotional response for each of those three elements, by using skin conductance, facial electromyography (EMG) and selfassessment scales....... The results show that packaging can elicit an emotional response via different elements. The paper also raises concerns about the accuracy of using selfreport measures of emotional responses to packaging research....

  8. Eliciting taxpayer preferences increases tax compliance

    OpenAIRE

    De Neve, Jan-Emmanuel; Lamberton, Cait; Norton, Michael I.

    2014-01-01

    Two experiments show that eliciting taxpayer preferences on government spending—providing taxpayer agency--increases tax compliance. We first create an income and taxation environment in a laboratory setting to test for compliance with a lab tax. Allowing a treatment group to express nonbinding preferences over tax spending priorities, leads to a 16% increase in tax compliance. A followup online study tests this treatment with a simulation of paying US federal taxes. Allowing taxpayers to sig...

  9. Unstructured Direct Elicitation of Decision Rules

    OpenAIRE

    Ding, Min; John R. Hauser; Dong, Songting; Dzyabura, Daria; Yang, Zhilin; Su, Chenting; Gaskin, Steven

    2010-01-01

    We investigate the feasibility of unstructured direct-elicitation (UDE) of decision rules consumers use to form consideration sets. With incentives to think hard and answer truthfully, tested formats ask respondents to state non-compensatory, compensatory, or mixed rules for agents who will select a product for the respondents. In a mobile-phone study two validation tasks (one delayed 3 weeks) ask respondents to indicate which of 32 mobile phones they would consider from a fractional 4[supers...

  10. Elicitation of secondary metabolism in actinomycetes

    OpenAIRE

    Abdelmohsen, Usama Ramadan; Grkovic, Tanja; Balasubramanian, Srikkanth; Kamel, Mohamed Salah; Quinn, Ronald J.; Hentschel, Ute

    2015-01-01

    Genomic sequence data have revealed the presence of a large fraction of putatively silent biosynthetic gene clusters in the genomes of actinomycetes that encode for secondary metabolites, which are not detected under standard fermentation conditions. This review focuses on the effects of biological (co-cultivation), chemical, as well as molecular elicitation on secondary metabolism in actinomycetes. Our review covers the literature until June 2014 and exemplifies the diversity of natural prod...

  11. A Paradigm for Eliciting Story Variation

    OpenAIRE

    Fisseni, Bernhard; Lawrence, Faith

    2013-01-01

    The understanding of story variation, whether motivated by cultural currents or other factors, is important for applications of formal models of narrative such as story generation or story retrieval. We present the first stage of an experiment to elicit natural narrative variation data suitable for evaluation with respect to story similarity, to qualitative and quantitative analysis of story variation, and also for data processing. We also present few prelimary results from the first stage of...

  12. Essays on probability elicitation scoring rules

    Science.gov (United States)

    Firmino, Paulo Renato A.; dos Santos Neto, Ademir B.

    2012-10-01

    In probability elicitation exercises it has been usual to considerer scoring rules (SRs) to measure the performance of experts when inferring about a given unknown, Θ, for which the true value, θ*, is (or will shortly be) known to the experimenter. Mathematically, SRs quantify the discrepancy between f(θ) (the distribution reflecting the expert's uncertainty about Θ) and d(θ), a zero-one indicator function of the observation θ*. Thus, a remarkable characteristic of SRs is to contrast expert's beliefs with the observation θ*. The present work aims at extending SRs concepts and formulas for the cases where Θ is aleatory, highlighting advantages of goodness-of-fit and entropy-like measures. Conceptually, it is argued that besides of evaluating the personal performance of the expert, SRs may also play a role when comparing the elicitation processes adopted to obtain f(θ). Mathematically, it is proposed to replace d(θ) by g(θ), the distribution that model the randomness of Θ, and do also considerer goodness-of-fit and entropylike metrics, leading to SRs that measure the adherence of f(θ) to g(θ). The implications of this alternative perspective are discussed and illustrated by means of case studies based on the simulation of controlled experiments. The usefulness of the proposed approach for evaluating the performance of experts and elicitation processes is investigated.

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

    Directory of Open Access Journals (Sweden)

    Davies M

    2014-02-01

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

  14. 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. PMID:8281355

  15. Review on immunotherapy in airway allergen sensitised patients.

    Science.gov (United States)

    van der Valk, J P M; de Jong, N W; Gerth van Wijk, R

    2015-07-01

    Allergen immunotherapy is a more than 100-year-old treatment in particular for birch pollen, grass pollen, house dust mite and cat dander sensitised allergic patients. The mechanism of allergen-specific immunotherapy is complex. Different hypotheses have been postulated to explain the mode of action, such as a decrease of the number of tissue mast cells, eosinophils and basophils, an increase of IgG4 and IgA synthesis, a shift from Th2 to Th1 cells and an increase in the number and function of IL-10 producing T-regulatory cells (T-reg). All these immunological effects may contribute to immune tolerance and long-term changes in the immune system. The efficacy and safety of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) with pollen and house dust mite have been investigated in many trials, meta-analyses and reviews. Nowadays grass pollen SLIT and SCIT, and birch pollen and house dust mite SCIT are implemented in clinical practice to treat therapy-resistant patients. However, the treatment is not effective for all patients and often not without side effects. Therefore, the development of new, safer and more effective immunotherapies is needed. These are approached along novel routes, including improved administration, combined treatment with immune response modifiers, fusion with immune response modifiers, allergen coupled to adjuvants and reconstruction of natural extracts with multiple recombinant allergens or with modified allergens. These developments are promising, but more research is required to implement them in clinical practice. PMID:26228190

  16. [Scleroderma related to specific immunotherapy. A report of a case].

    Science.gov (United States)

    Morfín Maciel, Blanca María; Castillo Morfín, Blanca María

    2009-01-01

    It has been described two main phenotypes of helper T cells. On activation, the immune system develops the most effective Th response. Whereas Th1 cells promote cell-mediate immunity against intracellular pathogens and an over expression could favor autoimmune diseases; Th2 cells develop humoral immunity against extracellular pathogens promoting allergic response. Normally, the two profiles coexist in the same individual with different grades of expression. Recently, it has been described a new subset: Th17, which is related to tissue injury in autoimmune diseases. Then, allergic and autoimmune diseases result from an unbalanced response of the immune system. Allergen-specific immunotherapy is the only curative treatment of a specific allergy, which leads to a life-long tolerance against allergens. There are no controlled studies about the effectiveness or risks associated with allergen-specific immunotherapy in patients with autoimmune disorders. On the other hand, scleroderma is an autoimmune chronic systemic disorder of unknown etiology characterized by excess collagen deposition in the skin and viscera, along with vascular injury. We report a girl with allergic asthma and with a second degree family history of systemic sclerosis who developed localized scleroderma during allergen specific immunotherapy. Because allergy vaccination alter the balance between effector and regulatory T-cell populations, which regulate immune tolerance, a positive family history of autoimmunity in first or second degree, could be a contraindication for allergen-specific immunotherapy. PMID:19768975

  17. 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. The...

  18. Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy

    Directory of Open Access Journals (Sweden)

    Stephanie L. Swift

    2016-02-01

    Full Text Available Large-scale assays, such as microarrays, next-generation sequencing and various “omics” technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and functionality within global populations or individual cells. Mapping immune changes over the course of oncolytic biotherapy—from initial infection to tumour stabilisation/regression through to long-term cure or escape/relapse—has the potential to generate important therapeutic insights around virus-host interactions. Further, correlating such immune signatures with specific tumour outcomes has significant value for guiding the development of novel oncolytic virus immunotherapy strategies. Here, we provide insights for OVIT from large-scale analyses of immune populations in the infection, vaccination and immunotherapy setting. We analyse several approaches to manipulating immune engagement during OVIT. We further explore immunocentric changes in the tumour tissue following immunotherapy, and compile several immune signatures of therapeutic success. Ultimately, we highlight clinically relevant large-scale approaches with the potential to strengthen future oncolytic strategies to optimally engage the immune system.

  19. Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy.

    Science.gov (United States)

    Swift, Stephanie L; Stojdl, David F

    2016-02-01

    Large-scale assays, such as microarrays, next-generation sequencing and various "omics" technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT) in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and functionality within global populations or individual cells. Mapping immune changes over the course of oncolytic biotherapy-from initial infection to tumour stabilisation/regression through to long-term cure or escape/relapse-has the potential to generate important therapeutic insights around virus-host interactions. Further, correlating such immune signatures with specific tumour outcomes has significant value for guiding the development of novel oncolytic virus immunotherapy strategies. Here, we provide insights for OVIT from large-scale analyses of immune populations in the infection, vaccination and immunotherapy setting. We analyse several approaches to manipulating immune engagement during OVIT. We further explore immunocentric changes in the tumour tissue following immunotherapy, and compile several immune signatures of therapeutic success. Ultimately, we highlight clinically relevant large-scale approaches with the potential to strengthen future oncolytic strategies to optimally engage the immune system. PMID:26861383

  20. Sublingual immunotherapy in youngsters : adherence in a randomized clinical trial

    NARCIS (Netherlands)

    Roder, E.; Berger, M. Y.; de Groot, H.; van Wijk, R. Gerth

    2008-01-01

    Background Adherence is essential for effective treatment. Although several trials on the efficacy of sublingual immunotherapy (SLIT) in youngsters have been published, few contain data on medication intake. Objective We aimed to quantify adherence both to study protocol and medication intake as wel

  1. 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....

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

    International Nuclear Information System (INIS)

    This study aimed to observe some of the mechanisms of allergen specific immunotherapy and to see if the idea of delayed Th2 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 CD95 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). CD95 was significantly increased in asthmatic patients denoting up regulation of the receptor on T-lymphocytes in asthmatics . The percent of CD95 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.

  3. [Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].

    Science.gov (United States)

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

    Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy. PMID:26469159

  4. Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy

    Science.gov (United States)

    Swift, Stephanie L.; Stojdl, David F.

    2016-01-01

    Large-scale assays, such as microarrays, next-generation sequencing and various “omics” technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT) in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and functionality within global populations or individual cells. Mapping immune changes over the course of oncolytic biotherapy—from initial infection to tumour stabilisation/regression through to long-term cure or escape/relapse—has the potential to generate important therapeutic insights around virus-host interactions. Further, correlating such immune signatures with specific tumour outcomes has significant value for guiding the development of novel oncolytic virus immunotherapy strategies. Here, we provide insights for OVIT from large-scale analyses of immune populations in the infection, vaccination and immunotherapy setting. We analyse several approaches to manipulating immune engagement during OVIT. We further explore immunocentric changes in the tumour tissue following immunotherapy, and compile several immune signatures of therapeutic success. Ultimately, we highlight clinically relevant large-scale approaches with the potential to strengthen future oncolytic strategies to optimally engage the immune system. PMID:26861383

  5. Development of nanoparticle based delivery systems for sublingual immunotherapy

    DEFF Research Database (Denmark)

    Alija, Hava; Rask, Carola; Brimnes, Jens

    The prevalence of IgE mediated allergic diseases is increasing dramatically in industrialized countries. Sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficacious treatment for IgE mediated allergic diseases, but requires protracted treatment duration. Even though SLIT is...

  6. Allergy immunotherapy prescribing trends for grass pollen-induced allergic rhinitis in Germany: a retrospective cohort analysis

    OpenAIRE

    McDonell, Amanda L; Wahn, Ulrich; Demuth, Dirk; Richards, Catrina; Hawes, Charlie; Andreasen, Jakob Nørgaard; Allen-Ramey, Felicia

    2015-01-01

    Background Allergy immunotherapy is an effective treatment for patients with allergic rhinitis whose symptoms are unresolved with pharmacotherapy. Allergy immunotherapy for grass pollen-induced allergic rhinitis is available in three modalities: subcutaneous immunotherapy and sublingual immunotherapy as a tablet or drop. This study aimed to understand trends in allergy immunotherapy prescribing and practice patterns for grass allergies in adult and paediatric patients in Germany. Methods A re...

  7. Systems biology applied to vaccine and immunotherapy development

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-09-01

    Full Text Available Abstract Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs plays in determining the nature and duration (immune memory of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology. In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment.

  8. Automated Preference Elicitation for Decision Making

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav

    Vol. 3. Berlin: Springer, 2013, s. 65-99. (Studies in Computational Intelligence. 474). ISBN 978-3-642-36405-1 R&D Projects: GA ČR GA13-13502S; GA ČR GA102/08/0567 Institutional research plan: CEZ:AV0Z1075907 Institutional support: RVO:67985556 Keywords : Bayesian decision making * fully probabilistic design * DM preference elicitation * support of imperfect participants Subject RIV: BC - Control Systems Theory http://library.utia.cas.cz/separaty/2013/AS/karny-0389631.pdf

  9. Isolated sleep paralysis elicited by sleep interruption.

    Science.gov (United States)

    Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K

    1992-06-01

    We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy. PMID:1621022

  10. 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

  11. Allergen immunotherapy for birch pollen-allergic patients: recent advances.

    Science.gov (United States)

    Moingeon, Philippe; Floch, Véronique Bordas-Le; Airouche, Sabi; Baron-Bodo, Véronique; Nony, Emmanuel; Mascarell, Laurent

    2016-05-01

    As of today, allergen immunotherapy is performed with aqueous natural allergen extracts. Recombinant allergen vaccines are not yet commercially available, although they could provide patients with well-defined and highly consistent drug substances. As Bet v 1 is the major allergen involved in birch pollen allergy, with more than 95% of patients sensitized to this allergen, pharmaceutical-grade recombinant Bet v 1-based vaccines were produced and clinically tested. Herein, we compare the clinical results and modes of action of treatments based on either a birch pollen extract or recombinant Bet v 1 expressed as hypoallergenic or natural-like molecules. We also discuss the future of allergen immunotherapy with improved drugs intended for birch pollen-allergic patients suffering from rhinoconjunctivitis. PMID:27140409

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

    International Nuclear Information System (INIS)

    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)

  13. Epigenetic modifiers in immunotherapy: a focus on checkpoint inhibitors.

    Science.gov (United States)

    Terranova-Barberio, Manuela; Thomas, Scott; Munster, Pamela N

    2016-06-01

    Immune surveillance should be directed to suppress tumor development and progression, involving a balance of coinhibitory and costimulatory signals that amplify immune response without overwhelming the host. Immunotherapy confers durable clinical benefit in 'immunogenic tumors', whereas in other tumors the responses are modest. Thus, immune checkpoint inhibitors may need to be combined with strategies to boost immune response or increase the tumor immune profile. Epigenetic aberrations contribute significantly to carcinogenesis. Recent findings suggest that epigenetic drugs prime the immune response by increasing expression of tumor-associated antigens and immune-related genes, as well as modulating chemokines and cytokines involved in immune system activation. This review describes our current understanding regarding epigenetic and immunotherapy combination, focusing on immune response priming to checkpoint blockade. PMID:27197539

  14. Immunotherapy of cancer with polymeric prodrugs: from dream to reality

    Czech Academy of Sciences Publication Activity Database

    Říhová, Blanka; Etrych, Tomáš; Kovář, Marek; Strohalm, Jiří; Kovář, Lubomír; Hovorka, Ondřej; Šírová, Milada; Plocová, Daniela; Chytil, Petr; Šubr, Vladimír; Ulbrich, Karel

    MALDEN : WILEY-BLACKWELL, 2009. s. 86-86. ISSN 1742-464X. [FEBS Congress "Life´s Molecular Interactions /34./. 04.07.2009-09.07.2009, Praha] R&D Projects: GA AV ČR KAN200200651; GA AV ČR IAAX00500803 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z40500505 Keywords : cancer * prodrugs * immunotherapy Subject RIV: EC - Immunology

  15. 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. PMID:26432911

  16. Current Clinical Trials Testing Combinations of Immunotherapy and Radiation

    OpenAIRE

    Crittenden, M.; Kohrt, H.; Levy, R.; Jones, J.; Camphausen, K.; Dicker, A.; Demaria, S.; Formenti, S.

    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 absco...

  17. T-cell regulatory mechanisms in specific immunotherapy

    OpenAIRE

    Jutel, M; Akdis, C. A.

    2008-01-01

    Allergen-specific immunotherapy (SIT) is the only treatment which leads to a lifelong tolerance against previously disease-causing allergens due to restoration of normal immunity against allergens. The description of T-regulatory (Treg) cells being involved in prevention of sensitization to allergens has led to great interest whether they represent a major target for allergen-SIT and whether it would be possible to manipulate Treg cells to increase its efficacy. Activationinduced cell death, ...

  18. Autoimmune myasthenia gravis, immunotherapy and thymectomy in children.

    Science.gov (United States)

    Ware, Tyson L; Ryan, Monique M; Kornberg, Andrew J

    2012-02-01

    Autoimmune myasthenia gravis is a rare condition in children. Identifying antibodies directed against the acetylcholine receptor is helpful in making the diagnosis. However, seronegative cases do exist and need to be distinguished from congenital forms of myasthenia. There is little published experience to inform the judicious management of autoimmune myasthenia gravis in children. In this article, we report our experience in the management of 12 cases of autoimmune myasthenia gravis in children in the modern era of medical immunotherapy and thymectomy. PMID:21911294

  19. ALLERGEN-SPECIFIC IMMUNOTHERAPY: VACCINES FOR ALLERGIC DISEASES

    OpenAIRE

    Fedorov, A. S.; L. S. Litvinova; V. I. But-Gusaim; S. N. Litvinenko

    2015-01-01

    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 treatmen...

  20. Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy

    OpenAIRE

    Chu, Dafeng; Zhao, Qi; Yu, Jian; Zhang, Faya; Zhang, Hui; Wang, Zhenjia

    2016-01-01

    Cancer immunotherapy using tumor specific monoclonal antibodies (mAbs) presents a novel approach for cancer treatment. A monoclonal antibody TA99 specific for gp75 antigen of melanoma, initiates neutrophil recruitment in tumor responsible for cancer therapy. Here we report a strategy for hijacking neutrophils in vivo using nanoparticles (NPs) to deliver therapeutics into tumor. In a mouse model of melanoma, we showed that systemically delivered albumin NPs increased in tumor when TA99 antibod...

  1. Novel allergen preparations for use in allergen-specific immunotherapy

    OpenAIRE

    Neimert Andersson, Theresa

    2008-01-01

    Allergy is a common disease in the industrialized countries, affecting approximately 25% of the population. Therefore, there is a need to find new treatment strategies to improve the quality of life for allergic individuals. Today the only treatment that gives long-lasting reduction of allergic symptoms is allergen-specific immunotherapy (SIT). However, despite successful clinical outcome, the method as it is performed today has some drawbacks such as therapy associated side...

  2. Skin Prick Testing and Immunotherapy in Nasobronchial Allergy: Our Experience

    OpenAIRE

    Lal, Amrith; Sunaina Waghray, Sunaina; Nand Kishore, N. N.

    2011-01-01

    In the present study of 331 patients suffering from signs/symptoms of nasal allergy, 9 nasal polyps, allergic conjunctivitis and allergic asthma, who were referred by clinician, were taken up for diagnosis of allergy with skin prick test (Ten et al. Mayo Clin Proc 70(8):783–784, 1995) and subjective improvement of patients by immunotherapy. Out of 331 patients tested 321 patients showed significant positive results and rest of them tested negative for allergy. High incidences of positive resu...

  3. Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy

    OpenAIRE

    Swift, Stephanie L.; Stojdl, David F

    2016-01-01

    Large-scale assays, such as microarrays, next-generation sequencing and various “omics” technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT) in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and funct...

  4. Subcutaneous Immunotherapy Improves the Symptomatology of Allergic Rhinitis

    OpenAIRE

    Lourenço, Edmir Américo; Caldeira, Eduardo José; Carvalho, César Alexandre Fabrega; Cunha, Marcelo Rodriques; Carvalho, Marcus Vinícius Henriques; Passos, Saulo Duarte

    2015-01-01

    Introduction The relevance of allergic rhinitis is unquestionable. This condition affects people's quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified a...

  5. The clinical-immunological analysis of a specific and combined immunotherapy of patients with cervical cancer

    OpenAIRE

    D. K. Kenbayeva; A. F. Lazarev

    2012-01-01

    Research objective is the comparative assessment of efficiency of two various ways of an immunotherapy of patients with cervical cancer. 57 patients with cervical cancer, the III stages, distributed on 3 groups – combined radiotherapy, a combination of a radiotherapy and specific immunotherapy, and also a radiotherapy, specific and adaptive immunotherapy are surveyed. Clinical efficiency of treatment was estimated by means of primary tumor regression and 3-year survival rate. The scheme of co...

  6. Immunotherapy for B-Cell Lymphoma: Current Status and Prospective Advances

    OpenAIRE

    Hollander, Nurit

    2012-01-01

    Therapy for non-Hodgkin’s lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of r...

  7. Needs Elicitation for Novel Pervasive Healthcare Technology

    DEFF Research Database (Denmark)

    Thorpe, Julia Rosemary; Forchhammer, B. H.; Maier, Anja

    2016-01-01

    inform designers about patients’ support needs and healthcare providers’ information needs.H ealthcare professionals offer a wealth of knowledge based on a clinical understanding of the condition as well as experience listening to patients' problems. Especially where patients are in denial about their......, and they are able to comment on trends, scale or proportions .We therefore explore how users' needs can be elicited by observing activities in which information is already being shared and discussed in the care process, and from the extensive knowledge of healthcare professionals. This is particularly...... include the large number of users required to represent the entire population. Failure to do so may lead to a solution that is over specialised to fit the needs of only a small subset of users. Both challenges are common in healthcare applications in which the end-user is also care recipient (or patient...

  8. Augmenting Usability: Cultural Elicitation in HCI

    Science.gov (United States)

    Camara, Souleymane Boundaouda; Oyugi, Cecilia; Abdelnour-Nocera, José; Smith, Andy

    This paper offers context and culture elicitation in an inter-cultural and multi-disciplinary setting of ICT design. Localised usability evaluation (LUE) is augmented with a socio-technical evaluation tool (STEM) as a methodological approach to expose and address issues in a collaborative ICT design within the Village e-Science for Life (VeSeL) project in rural Kenya. The paper argues that designers need to locally identify context and culture in situ and further explicate their implications through the design process and at the global level. Stakeholders' context, culture, decisions, agendas, expectations, disciplines and requirements need to be locally identified and globally evaluated to ensure a fit for purpose solution.

  9. 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.

  10. 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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Marc Mansour

    2011-08-01

    Full Text Available 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.

  13. 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.

  14. Immunotherapy of cancer employing adoptive T cell transfer

    Institute of Scientific and Technical Information of China (English)

    QIAOLI

    2005-01-01

    The current concept of“Adoptive T Cell Immunotherapy of Cancer”is quite different from how it was originally conceived.With the development of modern technology in molecular biology,cell biology,immunology and biochemistry during the last twenty years or so,adoptive immunotherapy has grown from its initial form of a simple“blood cell transfer”into its present process which involves host vauccination,effector cell activation/polarization and genetic modification.With the use of immune adjuvants and the identification/characterization of tumor-reactive T cell subsets,or in combination with other therapeutic strategies,adoptively transferred T cells have become much more potent inmediating tumor regression.In addition,studies on the trafficking of infused T cells,cell transfer performed in lymphopenic models,as well as the discovery of novel techniques in immune monitoring for the generation of effector cells in vitro and after cell transfer in vivo have provided useful tools to further improve the therapeutic efficacy of this approach.This article will review these related aspects of adoptive T cell immunotherapy of cancer with specific comments on certain critical areas in the application of this approach.With the rapidly evolving advances in this area,it is hoped that this cellular immunologic therapy as it was conceptualized in the past,can become more useful in the treatment of human cancer in the near future.

  15. Immunomonitoring in glioma immunotherapy: current status and future perspectives.

    Science.gov (United States)

    Lamano, Jonathan B; Ampie, Leonel; Choy, Winward; Kesavabhotla, Kartik; DiDomenico, Joseph D; Oyon, Daniel E; Parsa, Andrew T; Bloch, Orin

    2016-03-01

    Given the continued poor clinical outcomes and refractory nature of glioblastoma multiforme to traditional interventions, immunotherapy is gaining traction due to its potential for specific tumor-targeting and long-term antitumor protective surveillance. Currently, development of glioma immunotherapy relies on overall survival as an endpoint in clinical trials. However, the identification of surrogate immunologic biomarkers can accelerate the development of successful immunotherapeutic strategies. Immunomonitoring techniques possess the potential to elucidate immunological mechanisms of antitumor responses, monitor disease progression, evaluate therapeutic effect, identify candidates for immunotherapy, and serve as prognostic markers of clinical outcome. Current immunomonitoring assays assess delayed-type hypersensitivity, T cell proliferation, cytotoxic T-lymphocyte function, cytokine secretion profiles, antibody titers, and lymphocyte phenotypes. Yet, no single immunomonitoring technique can reliably predict outcomes, relegating immunological markers to exploratory endpoints. In response, the most recent immunomonitoring assays are incorporating emerging technologies and novel analysis techniques to approach the goal of identifying a competent immunological biomarker which predicts therapy responsiveness and clinical outcome. This review addresses the current status of immunomonitoring in glioma vaccine clinical trials with emphasis on correlations with clinical response. PMID:26638171

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

    International Nuclear Information System (INIS)

    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

  17. Sublingual allergen immunotherapy in HIV-positive patients.

    Science.gov (United States)

    Iemoli, E; Borgonovo, L; Fusi, A; Magni, C; Ricci, E D; Rizzardini, G; Piconi, S

    2016-03-01

    HIV infection is a relative contraindication for allergic immunotherapy (AIT). In the last decade, highly active antiretroviral therapy (HAART) has improved the immune function and life expectancy in HIV-infected patients whose respiratory allergic incidence is similar to the general population. We evaluated the safety and clinical effectiveness of sublingual immunotherapy in a group of grass pollen-allergic HAART-treated HIV-positive patients. Thirteen patients received sublingual immunotherapy (SLIT) tablet (Oralair, Stallergenes©) and symptomatic therapy and were compared with nine patients receiving symptomatic therapy alone. Clinical benefits were evaluated by the analysis of total combined score (TCS), sum of symptom-medication score, and a quality of life (QoL) questionnaire. HIV viral load and peripheral TCD4 lymphocytes were analyzed at the beginning and at the end of the study. Clinical efficacy data showed a significant improvement in SLIT-treated patients compared to controls (TCS: P = 0.0001; QoL: P = 0.03). We did not observe any significant alteration of TCD4 cell counts and viral load (VL) in both groups. Our preliminary data showed that SLIT therapy in viro-immunological controlled HAART treated HIV positive patients was efficacious, safe and well tolerated. PMID:26228482

  18. 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.

  19. The clinical-immunological analysis of a specific and combined immunotherapy of patients with cervical cancer

    Directory of Open Access Journals (Sweden)

    D. K. Kenbayeva

    2012-01-01

    Full Text Available Research objective is the comparative assessment of efficiency of two various ways of an immunotherapy of patients with cervical cancer. 57 patients with cervical cancer, the III stages, distributed on 3 groups – combined radiotherapy, a combination of a radiotherapy and specific immunotherapy, and also a radiotherapy, specific and adaptive immunotherapy are surveyed. Clinical efficiency of treatment was estimated by means of primary tumor regression and 3-year survival rate. The scheme of combined immunotherapy was shown to possess the most clinical efficiency. Positive dynamics of cell immunity indicators was accompanied to clinical efficiency of treatment.

  20. Investigating the Use of Audiovisual Elicitation on the Creative Enterprise

    OpenAIRE

    Flatt, Nicholas

    2014-01-01

    Elicitation methods have been explored extensively in social science research, and in business contexts, to uncover unarticulated informant knowledge. This qualitative study investigates the use of an audiovisual elicitation interviewing technique, developed by a UKbased creative multimedia production social enterprise; Fifth Planet Productions CIC. The method employs a system of using audiovisual stimulus to elicit participant responses in the interview setting. This study, conducted in t...

  1. Expert Elicitation of Population-Level Effects of Disturbance.

    Science.gov (United States)

    Fleishman, Erica; Burgman, Mark; Runge, Michael C; Schick, Robert S; Kraus, Scott

    2016-01-01

    Expert elicitation is a rigorous method for synthesizing expert knowledge to inform decision making and is reliable and practical when field data are limited. We evaluated the feasibility of applying expert elicitation to estimate population-level effects of disturbance on marine mammals. Diverse experts estimated parameters related to mortality and sublethal injury of North Atlantic right whales (Eubalaena glacialis). We are now eliciting expert knowledge on the movement of right whales among geographic regions to parameterize a spatial model of health. Expert elicitation complements methods such as simulation models or extrapolations from other species, sometimes with greater accuracy and less uncertainty. PMID:26610972

  2. Requirements for acquiring a high-quality house dust mite extract for allergen immunotherapy

    Directory of Open Access Journals (Sweden)

    Frati F

    2012-05-01

    Full Text Available Franco Frati,1 Cristoforo Incorvaia,2 Marie David,3 Silvia Scurati,3 Simona Seta,4 Guglielmo Padua,4 Eleonora Cattaneo,1 Carlo Cavaliere,5 Alessia Di Rienzo,6 Ilaria Dell'Albani,1 Paola Puccinelli11Medical and Scientific and Regulatory Department, Stallergenes, Milan, Italy; 2Allergy/Pulmonary Rehabilitation, ICP Hospital, Milan, Italy; 3Laboratoire Stallergenes, Antony, France; 4Marketing Department, Stallergenes, Milan, Italy; 5Ear, Nose and Throat Department, University Sapienza, Rome, Italy; 6Azienda Sanitaria Locale, Allergology Service, Frosinone, ItalyAbstract: The house dust mite is a major cause of respiratory allergy worldwide. The management of mite allergy is based on avoidance measures, drug treatment, and allergen immunotherapy, but only allergen immunotherapy is able to modify the natural history of the disease. Injectable subcutaneous immunotherapy was introduced a century ago, while sublingual immunotherapy was proposed in the 1980s and emerged in the ensuing years as an effective and safe option to subcutaneous immunotherapy. However, the quality of the extracts to be used in allergen immunotherapy is crucial for the success of treatment. The mite extract for sublingual immunotherapy known as Staloral 300 was developed to offer optimal characteristics concerning the mite culture medium, standardization, and allergen dose. Double-blind, placebo-controlled trials with Staloral 300 have provided a substantial part of the clinical evidence analyzed in a meta-analysis of the efficacy of allergen immunotherapy in mite-induced rhinitis and asthma. Safety and tolerability are very good, mild local reactions in the mouth being the most common side effect. This makes it feasible to carry out sublingual immunotherapy for the 3–5-year duration needed to achieve long-lasting tolerance to the specific allergen. The performance of Staloral 300 may provide optimal conditions for an effective and safe sublingual immunotherapy in patients with

  3. Acting green elicits a literal warm glow

    Science.gov (United States)

    Taufik, Danny; Bolderdijk, Jan Willem; Steg, Linda

    2015-01-01

    Environmental policies are often based on the assumption that people only act environmentally friendly if some extrinsic reward is implicated, usually money. We argue that people might also be motivated by intrinsic rewards: doing the right thing (such as acting environmentally friendly) elicits psychological rewards in the form of positive feelings, a phenomenon known as warm glow. Given the fact that people's psychological state may affect their thermal state, we expected that this warm glow could express itself quite literally: people who act environmentally friendly may perceive the temperature to be higher. In two studies, we found that people who learned they acted environmentally friendly perceived a higher temperature than people who learned they acted environmentally unfriendly. The underlying psychological mechanism pertains to the self-concept: learning you acted environmentally friendly signals to yourself that you are a good person. Together, our studies show that acting environmentally friendly can be psychologically rewarding, suggesting that appealing to intrinsic rewards can be an alternative way to encourage pro-environmental actions.

  4. Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a phase-1 study

    DEFF Research Database (Denmark)

    Larsen, T H; Poulsen, Lars K.; Melac, M;

    2006-01-01

    A single-centre, randomized, double-blind, placebo-controlled study. Aims: To compare the safety and tolerability of four different sublingual immunotherapy (SLIT) regimes in grass pollen allergic rhinitis.......A single-centre, randomized, double-blind, placebo-controlled study. Aims: To compare the safety and tolerability of four different sublingual immunotherapy (SLIT) regimes in grass pollen allergic rhinitis....

  5. 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

    2008-01-01

    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

  6. Priming the pancreatic cancer tumor microenvironment for checkpoint-inhibitor immunotherapy

    OpenAIRE

    Lutz, Eric R.; Kinkead, Heather; Jaffee, Elizabeth M.; Zheng, Lei

    2014-01-01

    Single agent immunotherapy is effective against several cancers, but has failed against poorly immunogenic cancers, including pancreatic cancer. Evaluation of pancreatic tumors following treatment with an experimental vaccine (Lutz et al. Cancer Immunology Research 2014) suggests that vaccination primes the tumor microenvironment (TME) for checkpoint-inhibitor immunotherapy, and supports a new platform for evaluating checkpoint-inhibitors in poorly immunogenic cancers.

  7. Introducing Forum Theatre to Elicit and Advocate Children's Views

    Science.gov (United States)

    Hammond, Nick

    2013-01-01

    Eliciting and advocating the voice of the child remains at the heart of international political agenda and also remains a central role for educational psychologists (EPs). Previous research indicates that EPs tend to use language-based methods for eliciting and advocating views of children. However, these approaches are often limited. Taking a…

  8. Elicited Emotions and Cognitive Functioning in Preschool Children

    Science.gov (United States)

    Blau, Rivka; Klein, Pnina S.

    2010-01-01

    In this study, the effects of eliciting positive and negative emotions on various cognitive functions of four- to five-year-old preschool children were examined. Emotions were elicited through presentations of "happy" and "sad" video clips, before the children performed the cognitive tasks. Behavioural (facial expressions) and physiological (heart…

  9. Belief elicitation in experiments: Is there a hedging problem?

    DEFF Research Database (Denmark)

    Blanco, Mariana; Engelmann, Dirk; Koch, Alexander;

    2010-01-01

    Belief-elicitation experiments usually reward accuracy of stated beliefs in addition to payments for other decisions. But this allows risk-averse subjects to hedge with their stated beliefs against adverse outcomes of the other decisions. So can we trust the existing belief-elicitation results? A...

  10. Science Teachers' Elicitation Practices: Insights for Formative Assessment

    Science.gov (United States)

    Ateh, Comfort M.

    2015-01-01

    In evaluating teachers' instructional decisions during instruction, it is clear that the nature of their elicitation is crucial for student learning. When instructional decisions are informed by information about students' conceptual understanding, significant learning is possible. This article examined the elicitation practices of two high school…

  11. Adherence issues related to sublingual immunotherapy as perceived by allergists

    Directory of Open Access Journals (Sweden)

    Silvia Scurati

    2010-06-01

    Full Text Available Silvia Scurati1, Franco Frati1, Gianni Passalacqua2, Paola Puccinelli1, Cecile Hilaire1, Cristoforo Incorvaia3, Italian Study Group on SLIT Compliance 1Scientific and Medical Department, Stallergenes, Milan, Italy; 2Allergy and Respiratory Diseases, Department of Internal Medicine, Genoa; 3Allergy/Pulmonary Rehabilitation, ICP Hospital, Milan, ItalyObjectives: Sublingual immunotherapy (SLIT is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence.Methods: We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10.Results: Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54% of allergists, followed by the possibility of reimbursement (ranked 1 by 34%, and by the absence of side effects (ranked 1 by 21%. Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20% of allergists.Conclusion: These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers.Keywords: adherence, sublingual immunotherapy, efficacy, cost, side effects

  12. The biochemical aftermath of anti-amyloid immunotherapy

    Directory of Open Access Journals (Sweden)

    Nicoll James AR

    2010-10-01

    Full Text Available Abstract Background Active and passive immunotherapy in both amyloid-beta precursor protein (APP transgenic mice and Alzheimer's Disease (AD patients have resulted in remarkable reductions in amyloid plaque accumulation, although the degree of amyloid regression has been highly variable. Nine individuals with a clinical diagnosis of AD dementia were actively immunized with the Aβ peptide 1-42 (AN-1792 and subjected to detailed postmortem biochemical analyses. These patients were compared to 6 non-immunized AD cases and 5 non-demented control (NDC cases. Results All patients were assessed for the presence of AD pathology including amyloid plaques, neurofibrillary tangles and vascular amyloidosis. This effort revealed that two immunotherapy recipients had dementia as a consequence of diseases other than AD. Direct neuropathological examination consistently demonstrated small to extensive areas in which amyloid plaques apparently were disrupted. Characterization of Aβ species remnants by ELISA suggested that total Aβ levels may have been reduced, although because the amounts of Aβ peptides among treated individuals were extremely variable, those data must be regarded as tentative. Chromatographic analysis and Western blots revealed abundant dimeric Aβ peptides. SELDI-TOF mass spectrometry demonstrated a substantive number of Aβ-related peptides, some of them with elongated C-terminal sequences. Pro-inflammatory TNF-α levels were significantly increased in the gray matter of immunized AD cases compared to the NDC and non-immunized AD groups. Conclusions Immunotherapy responses were characterized by extreme variability. Considering the broad range of biological variation that characterizes aging and complicates the recognition of reliable AD biomarkers, such disparities will make the interpretation of outcomes derived from epidemiologic and therapeutic investigations challenging. Although in some cases the apparent removal of amyloid plaques

  13. 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.

  14. Subcutaneous Immunotherapy Improves the Symptomatology of Allergic Rhinitis.

    Science.gov (United States)

    Lourenço, Edmir Américo; Caldeira, Eduardo José; Carvalho, César Alexandre Fabrega; Cunha, Marcelo Rodriques; Carvalho, Marcus Vinícius Henriques; Passos, Saulo Duarte

    2016-01-01

    Introduction The relevance of allergic rhinitis is unquestionable. This condition affects people's quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified allergens through puncture cutaneous tests using standardized extracts containing acari, fungi, pet hair, flower pollen, and feathers. Then, the patients underwent treatment with subcutaneous specific immunotherapy, using four vaccine vials for desensitization, associated with environmental hygiene. The authors analyzed conditions of nasal itching, sneeze, rhinorrhea, and nasal congestion throughout the treatment, and assigned them with a score ranging from zero (0), meaning absence of these symptoms to three (3), for severe cases. The symptoms were statistically compared in the beginning, during, and after treatment. Results In this study, authors analyzed the cases distribution according to age and the evolution of symptomatology according to the scores, comparing all phases of treatment. The average score for the entire population studied was 2.08 before treatment and 0.44 at the end. These results represent an overall improvement of ∼79% in symptomatology of allergic rhinitis in the studied population. Conclusion The subcutaneous immunotherapy as treatment of allergic rhinitis led to a reduction in all symptoms studied, improving the quality of life of patients, proving itself as an important therapeutic tool for these pathological conditions. PMID:26722338

  15. A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.

    Science.gov (United States)

    Li, Xuefang; Xu, Jian-Xin

    2016-10-01

    Pancreatic cancer is one of the most deadly types of cancer since it typically spreads rapidly and can seldom be detected in its early stage. Pancreatic cancer therapy is thus a challenging task, and appropriate prognosis or assessment for pancreatic cancer therapy is of critical importance. In this work, based on available clinical data in Niu et al. (2013) we develop a mathematical prognosis model that can predict the overall survival of pancreatic cancer patients who receive immunotherapy. The mathematical model incorporates pancreatic cancer cells, pancreatic stellate cells, three major classes of immune effector cells CD8+ T cells, natural killer cells, helper T cells, and two major classes of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ). The proposed model describes the dynamic interaction between tumor and immune cells. In order for the model to be able to generate appropriate prognostic results for disease progression, the distribution and stability properties of equilibria in the mathematical model are computed and analysed in absence of treatments. In addition, numerical simulations for disease progression with or without treatments are performed. It turns out that the median overall survival associated with CIK immunotherapy is prolonged from 7 to 13months compared with the survival without treatment, this is consistent with the clinical data observed in Niu et al. (2013). The validity of the proposed mathematical prognosis model is thus verified. Our study confirms that immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model. PMID:27338302

  16. Combination therapy with radiation and OK-432 immunotherapy of cancer patients

    International Nuclear Information System (INIS)

    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.)

  17. Targeting phospho-Ser422 by active Tau Immunotherapy in the THYTau22 mouse model: a suitable therapeutic approach. : Active Tau immunotherapy

    OpenAIRE

    Troquier, Laëticia; Caillierez, Raphaëlle; Burnouf, Sylvie; Fernandez-Gomez, Francisco,; Grosjean, Marie-Eve; Zommer, Nadège; Sergeant, Nicolas; Schraen-Maschke, Susanna; Blum, David; Buee, Luc

    2012-01-01

    Recent data indicate that Tau immunotherapy may be relevant for interfering with neurofibrillary degeneration in Alzheimer disease and related disorders referred to as Tauopathies. The key question for immunotherapy is the choice of the epitope to target. Abnormal phosphorylation is a well-described post-translational modification of Tau proteins and may be a good target. In the present study, we investigated the effects of active immunization against the pathological epitope phospho-Ser422 i...

  18. 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 the...... patient may not be sensitized. Recombinant allergens offer a possibility to use well defined molecules with consistent pharmaceutical quality defined in mass units. The proof of concept of the clinical efficacy of recombinant allergens is based on two studies published as full articles....

  19. Assays for predicting and monitoring responses to lung cancer immunotherapy

    OpenAIRE

    Teixidó, Cristina; Karachaliou, Niki; González-Cao, Maria; Morales-Espinosa, Daniela; Rosell, Rafael

    2015-01-01

    Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 (PD-1) and its ligand (PD-L1), have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer (NSCLC). Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting ...

  20. 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.

  1. Single-Chain Fragment Variable Passive Immunotherapies for Neurodegenerative Diseases

    OpenAIRE

    Liang Huang; Federoff, Howard J.; Xiaomin Su

    2013-01-01

    Accumulation of misfolded proteins has been implicated in a variety of neurodegenerative diseases including prion diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). In the past decade, single-chain fragment variable (scFv) -based immunotherapies have been developed to target abnormal proteins or various forms of protein aggregates including Aβ, SNCA, Htt, and PrP proteins. The scFvs are produced by fusing the variable regions of the antibody heavy and...

  2. Allergen immunotherapy for the prevention of allergic disease

    DEFF Research Database (Denmark)

    Dhami, Sangeeta; Nurmatov, Ulugbek; Halken, Susanne; Calderón, Moises A; Muraro, Antonella; Roberts, Graham; Du Toit, George; Kleine-Tebbe, Jörg; Larenas-Linnemann, Desiree; Lau, Susanne; Matricardi, Paolo Maria; Pajno, Giovanni; Papadopoulos, Nikolaos G; Pfaar, Oliver; Ryan, Dermot; Santos, Alexandra F; Timmermanns, Frans; Wahn, Ulrich; Sheikh, A

    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...... established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. DISCUSSION: The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT. This article is protected by copyright. All rights reserved....

  3. [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

    2016-03-01

    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

  4. 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.

  5. Allergen-specific immunotherapy in pediatric allergic asthma.

    Science.gov (United States)

    Yukselen, Ayfer

    2016-07-01

    Allergen-specific immunotherapy (AIT) is the only curative way that can change the immunologic response to allergens and thus can modify the natural progression of allergic diseases. There are some important criteria which contributes significantly on efficacy of AIT, such as the allergen extract used for treatment, the dose and protocol, patient selection in addition to the severity and control of asthma. The initiation of AIT in allergic asthma should be considered in intermittent, mild and moderate cases which coexisting with other allergic diseases such as allergic rhinitis, and in case of unacceptable adverse effects of medications. Two important impact of AIT; steroid sparing effect and preventing from progression to asthma should be taken into account in pediatric asthma when making a decision on starting of AIT. Uncontrolled asthma remains a significant risk factor for adverse events and asthma should be controlled both before and during administration of AIT. The evidence concerning the efficacy of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) for treatment of pediatric asthma suggested that SCIT decreases asthma symptoms and medication scores, whereas SLIT can ameliorate asthma symptoms. Although the effectiveness of SCIT has been shown for both seasonal and perennial allergens, the data for SLIT is less convincing for perennial allergies in pediatric asthma. PMID:27489785

  6. Advances in immunotherapy for non-small cell lung cancer.

    Science.gov (United States)

    Reckamp, Karen L

    2015-12-01

    In most patients, lung cancer presents as advanced disease with metastases to lymph nodes and/or distant organs, and survival is poor. Lung cancer is also a highly immune-suppressing malignancy with numerous methods to evade antitumor immune responses, including deficiencies in antigen processing and presentation, release of immunomodulatory cytokines, and inhibition of T-cell activation. Advances in understanding the complex interactions of the immune system and cancer have led to novel therapies that promote T-cell activation at the tumor site, resulting in prolonged clinical benefit. Immune checkpoint inhibitors, specifically programmed death receptor 1 pathway antibodies, have demonstrated impressively durable responses and improved survival in patients with non-small cell lung cancer. This article will review the recent progress made in immunotherapy for lung cancer with data from trials evaluating programmed death receptor 1 and cytotoxic T-lymphocyte-associated protein 4 monoclonal antibodies in addition to cancer vaccines. The review will focus on studies that have been published and the latest randomized trials exploring immune therapy in lung cancer. These results form the framework for a new direction in the treatment of lung cancer toward immunotherapy. PMID:27058851

  7. Immunotherapy of hepatoma with a monoclonal antibody against murine endoglin

    Institute of Scientific and Technical Information of China (English)

    Guang-Hong Tan; Feng-Ying Huang; Hua Wang; Yong-Hao Huang; Ying-Ying Lin; Yue-Nan Li

    2007-01-01

    AIM: To explore the capability of a monoclonal antibody(mAb) against murine endoglin to inhibit tumor angiogenesis and suppression of hepatoma growth in murine models.METHODS: A monoclonal antibody against murine endoglin was purified by affinity chromatography and passively transfused through tail veins in two murine hepatoma models. Tumor volume and survival time were observed at three-day intervals for 48 d. Microvessels in tumor tissues were detected by immunohistochemistry against CD31, and angiogenesis in vivo was determined by alginate encapsulated assay. In addition, tumor cell apoptosis was detected by TUNEL assay.RESULTS: Passive immunotherapy with anti-endoglin mAb could effectively suppress tumor growth, and prolonged the survival time of hepatoma-bearing mice.Angiogenesis was apparently inhibited within the tumor tissues, and the vascularization of alginate beads was also reduced in the mice passively transfused with antiendoglin mAb. In addition, increased apoptotic cells were observed within the tumor tissues from the mice passively transfused with anti-endoglin mAb.CONCLUSION: Passive immunotherapy with antiendoglin mAb effectively inhibits tumor growth via inhibiting tumor angiogenesis and increasing tumor cell apoptosis, which may be highly correlated with the blockage of endoglin-related signal pathway induced by anti-endoglin mAb.

  8. Potentiating Cancer Immunotherapy Using Papaya Mosaic Virus-Derived Nanoparticles.

    Science.gov (United States)

    Lebel, Marie-Ève; Chartrand, Karine; Tarrab, Esther; Savard, Pierre; Leclerc, Denis; Lamarre, Alain

    2016-03-01

    The recent development of novel immunotherapies is revolutionizing cancer treatment. These include, for example, immune checkpoint blockade, immunomodulation, or therapeutic vaccination. Although effective on their own, combining multiple approaches will most likely be required in order to achieve the maximal therapeutic benefit. In this regard, the papaya mosaic virus nanoparticle (PapMV) has shown tremendous potential as (i) an immunostimulatory molecule, (ii) an adjuvant, and (iii) a vaccine platform through its intrinsic capacity to activate the innate immune response in an IFN-α-dependent manner. Here, we demonstrate that intratumor administration of PapMV significantly slows down melanoma progression and prolongs survival. This correlates with enhanced chemokine and pro-inflammatory-cytokine production in the tumor and increased immune-cell infiltration. Proportions of total and tumor-specific CD8(+) T cells dramatically increase following PapMV treatment whereas those of myeloid-derived suppressor cells (MDSC) concomitantly decrease. Moreover, systemic PapMV administration prevents metastatic tumor-implantation in the lungs. Importantly, PapMV also synergistically improves the therapeutic benefit of dendritic cell (DC)-based vaccination and PD-1 blockade by potentiating antitumor immune responses. This study illustrates the immunostimulatory potential of a plant virus-derived nanoparticle for cancer therapy either alone or in conjunction with other promising immunotherapies in clinical development. PMID:26891174

  9. Immunotherapy with irradiated tumour cells and BCG in experimental osteosarcoma

    International Nuclear Information System (INIS)

    The effects of immunotherapy with irradiated tumour cells and BCG were studied in a non-metastasizing variety of the Dunn osteosarcoma transplantable in mice. Experimental animals which had been preimmunized with three injections of 0.7 to 1.4 x 106 irradiated tumour cells each 1 to 3 weeks before administration of 1 x 106 living tumour cells, showed a tumour incidence of 23 per cent. This was significantly (P<0.005) lower than the 92 per cent tumour incidence in the control animals. Non-specific immunotherapy with BCG given subcutaneously at a dose of 1.0 mg of dry-weight bacterial mass three times at 3-weeks intervals was found to have no protective effect against the osteosarcoma. The tumour incidence was 90 per cent for BCG-treated and 94 per cent for control animals. The osteosarcomas were studied light and electron microscopically and also with regard to the histochemical alkaline phosphatase activity. No structural difference was found between the tumours of the various groups. The demonstrated immunotherapeutic response is in contrast o the low degree of immunogenicity of the osteosarcoma, which we will report elsewhere. (author)

  10. Allergen-specific immunotherapy in pediatric allergic asthma

    Science.gov (United States)

    2016-01-01

    Allergen-specific immunotherapy (AIT) is the only curative way that can change the immunologic response to allergens and thus can modify the natural progression of allergic diseases. There are some important criteria which contributes significantly on efficacy of AIT, such as the allergen extract used for treatment, the dose and protocol, patient selection in addition to the severity and control of asthma. The initiation of AIT in allergic asthma should be considered in intermittent, mild and moderate cases which coexisting with other allergic diseases such as allergic rhinitis, and in case of unacceptable adverse effects of medications. Two important impact of AIT; steroid sparing effect and preventing from progression to asthma should be taken into account in pediatric asthma when making a decision on starting of AIT. Uncontrolled asthma remains a significant risk factor for adverse events and asthma should be controlled both before and during administration of AIT. The evidence concerning the efficacy of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) for treatment of pediatric asthma suggested that SCIT decreases asthma symptoms and medication scores, whereas SLIT can ameliorate asthma symptoms. Although the effectiveness of SCIT has been shown for both seasonal and perennial allergens, the data for SLIT is less convincing for perennial allergies in pediatric asthma. PMID:27489785

  11. The promising alliance of anti-cancer electrochemotherapy with immunotherapy.

    Science.gov (United States)

    Calvet, Christophe Y; Mir, Lluis M

    2016-06-01

    Anti-tumor electrochemotherapy, which consists in increasing anti-cancer drug uptake by means of electroporation, is now implanted in about 140 cancer treatment centers in Europe. Its use is supported by the English National Institute for Health and Care Excellence for the palliative treatment of skin metastases, and about 13,000 cancer patients were treated by this technology by the end of 2015. Efforts are now focused on turning this local anti-tumor treatment into a systemic one. Electrogenetherapy, that is the electroporation-mediated transfer of therapeutic genes, is currently under clinical evaluation and has brought excitement to enlarge the anti-cancer armamentarium. Among the promising electrogenetherapy strategies, DNA vaccination and cytokine-based immunotherapy aim at stimulating anti-tumor immunity. We review here the interests and state of development of both electrochemotherapy and electrogenetherapy. We then emphasize the potent beneficial outcome of the combination of electrochemotherapy with immunotherapy, such as immune checkpoint inhibitors or strategies based on electrogenetherapy, to simultaneously achieve excellent local debulking anti-tumor responses and systemic anti-metastatic effects. PMID:26993326

  12. CCSI Risk Estimation: An Application of Expert Elicitation

    Energy Technology Data Exchange (ETDEWEB)

    Engel, David W.; Dalton, Angela C.

    2012-10-01

    The Carbon Capture Simulation Initiative (CCSI) is a multi-laboratory simulation-driven effort to develop carbon capture technologies with the goal of accelerating commercialization and adoption in the near future. One of the key CCSI technical challenges is representing and quantifying the inherent uncertainty and risks associated with developing, testing, and deploying the technology in simulated and real operational settings. To address this challenge, the CCSI Element 7 team developed a holistic risk analysis and decision-making framework. The purpose of this report is to document the CCSI Element 7 structured systematic expert elicitation to identify additional risk factors. We review the significance of and established approaches to expert elicitation, describe the CCSI risk elicitation plan and implementation strategies, and conclude by discussing the next steps and highlighting the contribution of risk elicitation toward the achievement of the overarching CCSI objectives.

  13. Utilizing online serious games to facilitate distributed requirements elicitation

    OpenAIRE

    Ghanbari, Hadi; Similä, Jouni; Markkula, Jouni

    2015-01-01

    Requirements elicitation is one of the most important and challenging activities in software development projects. A variety of challenges related to requirements elicitation are reported in the literature, of which the lack of proper communication and knowledge transfer between software stakeholders are among the most important. Communication and knowledge transfer are becoming even bigger challenges with the current increase in globally distributed software development projects due to the t...

  14. Elicitation of normative and fairness judgments: Do incentives matter?

    OpenAIRE

    Štěpán Veselý

    2015-01-01

    Krupka and Weber (2013) introduce an incentive-compatible coordination game as an alternative method for elicitation of normative judgments. I show, however, that people provide virtually the same responses in incentivized and non-incentivized versions of the Krupka-Weber game. Besides ratings of social appropriateness, I also elicit ratings of fairness of all possible offers in an ultimatum game. Ratings of social appropriateness and fairness are similar for low offers (bel...

  15. The new vaccines: building viruses that elicit antitumor immunity

    OpenAIRE

    Restifo, Nicholas P

    1996-01-01

    Whereas cancer cells are poor immunogens, some viruses are capable of eliciting powerful and lifelong immunity. Recombinant viruses and plasmid DNA encoding tumor-associated antigens can elicit powerful and specific immune responses that can be enhanced by the use of cytokines and costimulatory molecules. These immune responses have destroyed growing tumor cells in experimental animal models. For the first time, immunotherapeutic strategies that employ recombinant viruses are being tested in ...

  16. Elicitation of preferences for improvements in ostomy pouches

    DEFF Research Database (Denmark)

    Bonnichsen, Ole

    This paper attempts to examine and measure ostomates’ preferences for improvements in ostomy pouches. Described are the study design, elicitation procedure and resulting preference structure of the Swedish ostomate sample. The method used to elicit the preferences is a Discrete Choice Experiment ......, emphasis should be placed on this attribute when decisions are made as to the allocation of scarce health care resources within research and development aimed at improving ostomy pouches....

  17. Structured Language Requirement Elicitation Using Case Base Reasoning

    OpenAIRE

    Marryam Murtaza; Jamal Hussain Shah; Aisha Azeem; Wasif Nisar; Maria Masood

    2013-01-01

    Requirement elicitation is very difficult process in highly challenging and business based software as well as in real time software. Common problems associated with these types of software are rapidly changing the requirements and understanding the language of the layman person. In this study, a framework for requirement elicitation by using knowledge based system is proposed, which is very helpful for knowledge documentation, intelligent decision support, self-learning and more specifically...

  18. NVC Based Model for Selecting Effective Requirement Elicitation Technique

    Directory of Open Access Journals (Sweden)

    Md. Rizwan Beg

    2012-10-01

    Full Text Available Requirement Engineering process starts from gathering of requirements i.e.; requirements elicitation. Requirementselicitation (RE is the base building block for a software project and has very high impact onsubsequent design and builds phases as well. Accurately capturing system requirements is the major factorin the failure of most of software projects. Due to the criticality and impact of this phase, it is very importantto perform the requirements elicitation in no less than a perfect manner. One of the most difficult jobsfor elicitor is to select appropriate technique for eliciting the requirement. Interviewing and Interactingstakeholder during Elicitation process is a communication intensive activity involves Verbal and Nonverbalcommunication (NVC. Elicitor should give emphasis to Non-verbal communication along with verbalcommunication so that requirements recorded more efficiently and effectively. In this paper we proposea model in which stakeholders are classified by observing non-verbal communication and use it as a basefor elicitation technique selection. We also propose an efficient plan for requirements elicitation which intendsto overcome on the constraints, faced by elicitor.

  19. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    Science.gov (United States)

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit. PMID:26250412

  20. Challenges and future perspectives of T cell immunotherapy in cancer.

    Science.gov (United States)

    de Aquino, Maria Teresa P; Malhotra, Anshu; Mishra, Manoj K; Shanker, Anil

    2015-08-01

    Since the formulation of the tumour immunosurveillance theory, considerable focus has been on enhancing the effectiveness of host antitumour immunity, particularly with respect to T cells. A cancer evades or alters the host immune response by various ways to ensure its development and survival. These include modifications of the immune cell metabolism and T cell signalling. An inhibitory cytokine milieu in the tumour microenvironment also leads to immune suppression and tumour progression within a host. This review traces the development in the field and attempts to summarize the hurdles that the approach of adoptive T cell immunotherapy against cancer faces, and discusses the conditions that must be improved to allow effective eradication of cancer. PMID:26096822

  1. Topical immunotherapy with diphenylcyclopropenone in vitiligo: A preliminary experience

    Directory of Open Access Journals (Sweden)

    Aghaei Shahin

    2008-01-01

    Full Text Available Background: Despite recent significant therapeutic advances, vitiligo remains a clinical conundrum. Topical immunotherapy has been extensively tested in the treatment of various dermatologic disorders, especially those believed to have an immunologic basis. Aim: To evaluate the role of topical diphenylcyclopropenone (DPCP in the treatment of vitiligo. Methods: Nineteen patients with limited vitiligo lesions were enrolled in this study. After sensitization with 2% lotion of DPCP in acetone, progressively higher concentrations beginning at 0.001% up to 2% were applied weekly for 6 months to the depigmented skin lesions. Results: Thirteen of the 19 patients were evaluated at the end of 6 months. Four patients with focal vitiligo, one patient with vitiligo vulgaris, and three patients with segmental vitiligo showed marked (grade 3 repigmentation. Conclusion: Marginal and central repigmentation with hyperpigmented borders was seen in the majority of lesions. Further controlled trials should be undertaken to evaluate the use of topical DPCP in vitiligo.

  2. Checkpoint Blockade in Cancer Immunotherapy: Squaring the Circle

    Directory of Open Access Journals (Sweden)

    Maria A.V. Marzolini

    2015-03-01

    Full Text Available Manipulating the complex interaction between the immune system and tumour cells has been the focus of cancer research for many years, but it is only in the past decade that significant progress has been made in the field of cancer immunotherapy resulting in clinically effective treatments. The blockade of co-inhibitory immune checkpoints, essential for maintaining lymphocyte homeostasis and self-tolerance, by immunomodulatory monoclonal antibodies has resulted in the augmentation of anti-tumour responses. The greatest successes so far have been seen with the blockade of cytotoxic T lymphocyte associated antigen-4, which has resulted in the first Phase III clinical trial showing an overall survival benefit in metastatic melanoma, and in the blockade of the programmed cell death protein-1 axis. This concise review will focus on the clinical advances made by the blockade of these two pathways and their role in current cancer treatment strategies.

  3. Immune response to HHV-6 and implications for immunotherapy.

    Science.gov (United States)

    Becerra, Aniuska; Gibson, Laura; Stern, Lawrence J; Calvo-Calle, J Mauricio

    2014-12-01

    Most adults remain chronically infected with HHV-6 after resolution of a primary infection in childhood, with the latent virus held in check by the immune system. Iatrogenic immunosuppression following solid organ transplantation (SOT) or hematopoetic stem cell transplantation (HSCT) can allow latent viruses to reactivate. HHV-6 reactivation has been associated with increased morbidity, graft rejection, and neurological complications post-transplantation. Recent work has identified HHV-6 antigens that are targeted by the CD4+ and CD8+ T cell response in chronically infected adults. T cell populations recognizing these targets can be expanded in vitro and are being developed for use in autologous immunotherapy to control post-transplantation HHV-6 reaction. PMID:25462448

  4. Immunotherapy as a Potential Treatment for Chordoma: a Review.

    Science.gov (United States)

    Patel, Shalin S; Schwab, Joseph H

    2016-09-01

    Chordoma is a locally aggressive primary malignancy of the axial skeleton. The gold standard for treatment is en bloc resection, with some centers now advocating for the use of radiation to help mitigate the risk of recurrence. Local recurrence is common, and salvaging local failures is quite difficult. Chemotherapy has been ineffective and small molecule targeted therapy has had only marginal benefits in small subsets of patients with rare tumor phenotypes or refractory disease. Recent successes utilizing immunotherapy in a variety of cancers has led to a resurgence of interest in modifying the host immune system to develop new ways to treat tumors. This review will discuss these studies and will highlight the early studies employing immune strategies for the treatment of chordoma. PMID:27475804

  5. Food allergy to apple and specific immunotherapy with birch pollen

    DEFF Research Database (Denmark)

    Hansen, Kirsten Skamstrup; Khinchi, Marianne Søndergaard; Skov, Per Stahl;

    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...... (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in......-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...

  6. Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy

    Science.gov (United States)

    Chu, Dafeng; Zhao, Qi; Yu, Jian; Zhang, Faya; Zhang, Hui; Wang, Zhenjia

    2016-01-01

    Cancer immunotherapy using tumor specific monoclonal antibodies (mAbs) presents a novel approach for cancer treatment. A monoclonal antibody TA99 specific for gp75 antigen of melanoma, initiates neutrophil recruitment in tumor responsible for cancer therapy. Here we report a strategy for hijacking neutrophils in vivo using nanoparticles (NPs) to deliver therapeutics into tumor. In a mouse model of melanoma, we showed that systemically delivered albumin NPs increased in tumor when TA99 antibody was injected; and the nanoparticle tumor accumulation was mediated by neutrophils. After the administration of pyropheophorbide-a (Ppa) loaded albumin NPs and TA99, photodynamic therapy significantly suppressed the tumor growth and increased mouse survival compared with treatment with the NPs or TA99. The study reveals a new avenue to treat cancer by nanoparticle hitchhiking of immune systems to enhance delivery of therapeutics into tumor sites. PMID:26989887

  7. Indoleamine 2, 3-dioxygenase: potential in cancer immunotherapy

    International Nuclear Information System (INIS)

    Indoleamine 2, 3-dioxygenase (IDO) is a potent immunosuppressive enzyme that has a significant role in different types of cancers. There is evidence that shows its involvement in a number of infectious diseases and auto-immune disorders. In vitro and in vivo studies indicate that 1-methyl tryptophan, being a competitive inhibitor, has shown to actively control the conditions in which IDO is over-expressed. Dendritic cells are the natural site of secretion of IDO in the host immune system. However, the expression takes place only in the presence of tolerogenic signals that lead to suppression of T-cell mediated immunogenic responses. Different therapies are being designed by employing the role of IDO in conditions such as stress, depression, cancer, pregnancy, and organ transplant, which reflect the promising role of this new target in cancer immunotherapy. (author)

  8. Allergen extracts for immunotherapy: to mix or not to mix?

    Science.gov (United States)

    Nony, Emmanuel; Martelet, Armelle; Jain, Karine; Moingeon, Philippe

    2016-03-01

    Allergen immunotherapy (AIT) is established as a curative treatment for allergic rhinitis, asthma, as well as insect venom allergy. AIT is based on the administration of natural allergen extracts via the subcutaneous or sublingual routes to reorient the immune system towards tolerogenic mechanisms. In this regard, since many patients are poly-allergic, mixtures of allergen extracts are often used with a potential risk to cause allergen degradation, thereby affecting treatment efficacy. Herein, we discuss the advantages and drawbacks of mixing homologous (i.e., related) or heterogeneous (i.e., unrelated) allergen extracts. We provide evidence for incompatibilities between mixes of grass pollen and house dust mite extracts containing bodies and feces, and summarize critical points to consider when mixing allergen extracts for AIT. PMID:26652799

  9. A mathematical model of the dynamics of antitumor laser immunotherapy

    Science.gov (United States)

    Dawkins, Bryan A.; Laverty, Sean M.

    2014-02-01

    We use a mathematical model to describe and predict the population dynamics of tumor cells, immune cells, and other immune components in a host undergoing laser immunotherapy treatment against metastatic cancer. We incorporate key elements of the treatment into the model: a function describing the laser-induced primary tumor cell death and parameters capturing the role and strength of the primary immunoadjuvant, glycated chitosan. We focus on identifying conditions that ensure a successful treatment. In particular, we study the patient response (i.e., anti-tumor immune dynamics and treatment outcome) in two different but related mathematical models as we vary quantitative features of the immune system (supply, proliferation, death, and interaction rates). We compare immune dynamics of a `baseline' immune model against an `augmented' model (with additional cell types and antibodies) and in both, we find that using strong immunoadjuvants, like glycated chitosan, that enhance dendritic cell activity yields more promising patient outcomes.

  10. 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...... still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens and the...... appropriate co-stimulatory molecules required for T-cell activation. Initially tested in animal models, this approach has now been evaluated in clinical trials, although with limited success. We summarize and discuss the results from the animal studies and first clinical trials. We also present a new approach...

  11. Stinging insect allergy: current perspectives on venom immunotherapy

    Directory of Open Access Journals (Sweden)

    Ludman SW

    2015-07-01

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

  12. "Evaluation of Six Years Allergen Immunotherapy in Allergic Rhinitis and Allergic Asthma "

    Directory of Open Access Journals (Sweden)

    "Reza Farid

    2006-03-01

    Full Text Available Allergen immunotherapy involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. In the present study we evaluated a period of six years immunotherapy allergic rhinitis and allergic asthma patients with positive skin prick test of common aeroallergen. The immunotherapy was performed on 156 patients. One hundred twenty of the cases were allergic rhinitis (80%, 29 cases had allergic asthma and 7 cases were mixed (4.5%. 70% in allergic rhinitis group, 75% in allergic asthma group and 42.8% in mixed group completely improved. Immunotherapy, an older therapeutic method, has now been updated, and with appropriate indications, precautions and methods, has been clearly shown to be effective in the treatment of allergic rhinitis and in some cases of asthma and insect hypersensitivity.

  13. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients

    DEFF Research Database (Denmark)

    Howarth, P; Malling, Hans-Jørgen; Molimard, M; Devillier, P

    2011-01-01

    To cite this article: Howarth P, Malling H-J, Molimard M, Devillier P. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients. Allergy 2012; 67: 321-327. ABSTRACT: Background:  The assessment of allergen immunotherapy (AIT) efficacy in the...... treatment for seasonal allergic rhinoconjunctivitis (SAR) symptoms is challenging. Allergen immunotherapy differs from symptomatic therapy in that while symptomatic therapy treats patients after symptoms appear and aims to reduce symptoms, AIT is administered before symptoms are present and aims to prevent...... them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective of...

  14. Interleukin-2 based immunotherapy in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Donskov, Frede

    2007-01-01

    neutrophils >6.0) were independent prognostic factors of short survival in patients with mRCC receiving IL-2, identifying subgroups with estimated 5-year survival rates of 60%, 25% and 0%, respectively. These features may help to select patients more likely to benefit from IL-2 based immunotherapy......The present thesis consists of 8 published articles focusing on interleukin-2 based immunotherapy in metastatic renal cell carcinoma (mRCC). This disease represents a significant challenge, as the tumor is resistant to current chemotherapy, hormonal therapy and radiation therapy. However, IL-2...... were harmful for the outcome of IL-2 based immunotherapy. In progressing patients, the leukocyte subsets in blood and tumor tissue remained unaffected by cytokine therapy. The fate of a patient with mRCC prior to IL-2 and IFN-alpha based immunotherapy cannot be determined by measuring baseline tumor...

  15. Immunotherapy for non-small cell lung cancer: current concepts and clinical trials.

    Science.gov (United States)

    Mayor, Marissa; Yang, Neng; Sterman, Daniel; Jones, David R; Adusumilli, Prasad S

    2016-05-01

    Recent successes in immunotherapeutic strategies are being investigated to combat cancers that have less than ideal responses to standard of care treatment, such as non-small-cell lung cancer. In this paper, we summarize concepts and the current status of immunotherapy for non-small cell lung cancer, including salient features of the major categories of immunotherapy-monoclonal antibody therapy, immune checkpoint blockade, immunotoxins, anticancer vaccines, and adoptive cell therapy. PMID:26516195

  16. Quality of Life Improvement with Sublingual Immunotherapy: A Prospective Study of Efficacy

    OpenAIRE

    Mary S. Morris; Amanda Lowery; Theodoropoulos, Demetrios S.; R. Daniel Duquette; Morris, David L

    2012-01-01

    Due to its excellent safety profile, ease of administration, and economic considerations, sublingual immunotherapy (SLIT) is becoming a preferred form of allergen specific immunotherapy. The efficacy of SLIT is still debated. The purpose of this act of practice trial is to evaluate quality of life outcomes in patients treated with SLIT. Fifty one patients with allergic rhinoconjunctivitis demonstrated by skin testing completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at in...

  17. Design of tumor-specific immunotherapies using dendritic cells - effect of bromelain on dendritic cell maturation

    OpenAIRE

    Karlsen, Marie

    2009-01-01

    Immunotherapy using dendritic cells (DC) has shown promising results in clinical trials, but few relevant successes are recorded. Therefore, the choice of an appropriate DC population is critical for the outcome of this treatment. The DC used today in immunotherapy are often matured with a cytokine cocktail consisting of TNF-α, IL-1β, IL-6 and PGE2. These cells have deficits in their cytokine production, and also their migratory capacity in vivo needs improvement. After being introduced to br...

  18. Effects of surgery, immunization, and laser immunotherapy on a non-immunogenic metastic tumor model

    Science.gov (United States)

    Chen, Wei R.; Huang, Zheng; Andrienko, Kirill; Stefanov, Stefan; Wolf, Roman F.; Liu, Hong

    2006-08-01

    Traditional local cancer treatment modalities include surgery and radiation, which has the immediate tumor response due to tumor removal or radiation induced cell death. However, such therapeutic approaches usually do not result in eradiation of tumors, particularly when treating metastatic tumors. In fact, local treatment of primary tumors may stimulate the growth and spread of remote metastasis. Commonly used systemic therapies include chemotherapy and immunotherapy, which target the dividing cells or the immune systems. However, in addition to the severe side effects, chemotherapy often suppresses the immune systems, hence lessening the host's ability to fight the disease. Immunotherapy, on the other hand, aims at educating and stimulating immune systems using either general immune enhancements or antigen-oriented specific immune stimulation. However, so far, the traditional immunotherapy has yielded only limited success in treating cancer patients. A different approach is needed. To combine the advantages of both local therapies for acute and targeted treatment responses and the systemic therapies for stimulation of the immune systems, laser immunotherapy was proposed to use selective photothermal therapy as the local treatment modality and the adjuvant-assisted immunotherapy for systemic control. Laser immunotherapy has show positive results in treating metastatic tumors. In this study, we conducted a comparative study using surgery, freeze-thaw immunization and laser immunotherapy in the treatment of metastatic rat mammary tumors. Our results showed that removal of the primary tumors was unsuccessful at changing the course of tumor progression. The tumor cell lysate immunization delayed the emergence of metastases but did not provide immunity against the tumor challenge. Laser immunotherapy, on the other hand, resulted in regression and eradication.

  19. Immunotherapy for B-cell lymphoma: current status and prospective advances.

    Science.gov (United States)

    Hollander, Nurit

    2012-01-01

    Therapy for non-Hodgkin's lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of rituximab catalyzed the development of new passive immunotherapy strategies that are currently undergoing clinical evaluation. These include improvement of rituximab efficacy, newer generation anti-CD20 antibodies, drug-conjugated and radio labeled anti-CD20 antibodies, monoclonal antibodies targeting non-CD20 lymphoma antigens, and bispecific antibodies. Active immunotherapy aims at inducing long-lasting antitumor immunity, thereby limiting the likelihood of relapse. Current clinical studies of active immunotherapy for lymphoma consist largely of vaccination and immune checkpoint blockade. A variety of protein- and cell-based vaccines are being tested in ongoing clinical studies. Recently completed phase III clinical trials of an idiotype protein vaccine suggest that the vaccine may have clinical activity in a subset of patients. Efforts to enhance the efficacy of active immunotherapy are ongoing with an emphasis on optimization of antigen delivery and presentation of vaccines and modulation of the immune system toward counteracting immunosuppression, using antibodies against immune regulatory checkpoints. This article discusses results of the various immunotherapy approaches applied to date for B-cell lymphoma and the ongoing trials to improve their effect. PMID:22566889

  20. Immunotherapy for B-cell lymphoma: current status and prospective advances

    Directory of Open Access Journals (Sweden)

    Nurit eHollander

    2012-01-01

    Full Text Available Therapy for non-Hodgkin's lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of rituximab catalyzed the development of new passive immunotherapy strategies that are currently undergoing clinical evaluation. These include improvement of rituximab efficacy, newer generation anti-CD20 antibodies, drug-conjugated and radiolabelled anti-CD20 antibodies, monoclonal antibodies targeting non-CD20 lymphoma antigens, and bispecific antibodies. Active immunotherapy aims at inducing long-lasting antitumor immunity, thereby limiting the likelihood of relapse. Current clinical studies of active immunotherapy for lymphoma consist largely of vaccination and immune checkpoint blockade. A variety of protein- and cell-based vaccines are being tested in ongoing clinical studies. Recently completed phase III clinical trials of an idiotype protein vaccine suggest that the vaccine may have clinical activity in a subset of patients. Efforts to enhance the efficacy of active immunotherapy are ongoing with an emphasis on optimization of antigen delivery and presentation of vaccines and modulation of the immune system toward counteracting immunosuppression, using antibodies against immune regulatory checkpoints. This article discusses results of the various immunotherapy approaches applied to date for B-cell lymphoma and the ongoing trials to improve their effect.

  1. 2015 Guidance on cancer immunotherapy development in early‐phase clinical studies

    OpenAIRE

    ,; Arato, Teruyo; Daimon, Takashi; Heike, Yuji; Ishii, Ken; Itho, Kyogo; KAGEYAMA, SHINICHI; Kawakami, Yutaka; Nakayama, Eiichi; Ozawa, Keiya; Sato, Noriyuki; Shiku, Hiroshi; Takeuchi, Masahiro; Tani, Kenzaburo; Tamada, Koji

    2015-01-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of “cancer vaccines”, which are based on the idea of vaccination, “effector cell therapy”, classified as passive immunotherapy, and “inhibition of immunosuppression”, which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune check...

  2. Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review.

    Science.gov (United States)

    Röder, Esther; Berger, Marjolein Y; de Groot, Hans; van Wijk, Roy Gerth

    2008-05-01

    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 the efficacy of immunotherapy in all its different administration forms in youngsters. Therefore, we systematically reviewed randomized controlled trials (RCTs) to evaluate the effect of immunotherapy with inhalant allergens on symptoms and medication use in children and adolescents with allergic rhinoconjunctivitis. Medline, EMBASE, the Cochrane Controlled Clinical Trials Register and reference lists of recent reviews and published trials were searched. RCTs including youngsters aged 0-18 yr with allergic rhinoconjunctivitis and comparing immunotherapy with placebo, symptomatic treatment or a different administration form of immunotherapy were included. Primary outcome measures were rhinoconjunctivitis symptom and/or medication scores. Methodological quality was assessed using the validated Delphi list. A method of best evidence synthesis, a rating system with levels of evidence based on the overall quality and the outcome of the trials, was used to assess efficacy. Six subcutaneous (SCIT), four nasal (LNIT), seven oral (OIT) and 11 sublingual (SLIT) immunotherapy trials, comprising 1619 youngsters, were included. Only 39% of the trials were of high methodological quality. For the SCIT and OIT subgroups the level of evidence for efficacy was conflicting. Moderate evidence of effect was found for LNIT. Analysis of the SLIT subgroup showed no evidence of effect. The evidence for the perennial and seasonal allergen trials within the subgroups varied from moderate evidence of effect to no evidence of effect. In conclusion, there is at present insufficient evidence that immunotherapy in any administration form has a positive effect on symptoms and/or medication use in

  3. Oral and sublingual immunotherapy for food allergy: current progress and future directions

    OpenAIRE

    Moran, Timothy P.; Vickery, Brian P.; Burks, A. Wesley

    2013-01-01

    Food allergies are increasing in prevalence and present an emerging epidemic for westernized countries. Strict dietary avoidance is the only approved management for food allergy, but accidental exposures regularly occur, leading to significant patient anxiety and decreased quality of life. Over the past decade, oral and sublingual immunotherapies have emerged as potential treatments for food allergy. While several small clinical trials have demonstrated that immunotherapy can desensitize food...

  4. Rationale for a multimodality strategy to enhance the efficacy of dendritic cell-based cancer immunotherapy

    OpenAIRE

    Jashodeep eDatta; Erik eBerk; Jessica A Cintolo; Shuwen eXu; Roses, Robert E; Czerniecki, Brian J.

    2015-01-01

    Dendritic cells (DC), master antigen-presenting cells that orchestrate interactions between the adaptive and innate immune arms, are increasingly utilized in cancer immunotherapy. Despite remarkable progress in our understanding of DC immunobiology, as well as several encouraging clinical applications — such as DC-based sipuleucel-T for metastatic castration-resistant prostate cancer — clinically effective DC-based immunotherapy as monotherapy for a majority of tumors remains a distant goal. ...

  5. Rationale for a Multimodality Strategy to Enhance the Efficacy of Dendritic Cell-Based Cancer Immunotherapy

    OpenAIRE

    Datta, Jashodeep; Berk, Erik; Jessica A Cintolo; Xu, Shuwen; Roses, Robert E; Czerniecki, Brian J.

    2015-01-01

    Dendritic cells (DC), master antigen-presenting cells that orchestrate interactions between the adaptive and innate immune arms, are increasingly utilized in cancer immunotherapy. Despite remarkable progress in our understanding of DC immunobiology, as well as several encouraging clinical applications – such as DC-based sipuleucel-T for metastatic castration-resistant prostate cancer – clinically effective DC-based immunotherapy as monotherapy for a majority of tumors remains a distant goal. ...

  6. Endoplasmic reticulum chaperone glucose regulated protein 170-Pokemon complexes elicit a robust antitumor immune response in vivo.

    Science.gov (United States)

    Yuan, Bangqing; Xian, Ronghua; Wu, Xianqu; Jing, Junjie; Chen, Kangning; Liu, Guojun; Zhou, Zhenhua

    2012-07-01

    Previous evidence suggested that the stress protein grp170 can function as a highly efficient molecular chaperone, binding to large protein substrates and acting as a potent vaccine against specific tumors when purified from the same tumor. In addition, Pokemon can be found in almost all malignant tumor cells and is regarded to be a promising candidate for the treatment of tumors. However, the potential of the grp170-Pokemon chaperone complex has not been well described. In the present study, the natural chaperone complex between grp170 and the Pokemon was formed by heat shock, and its immunogenicity was detected by ELISPOT and (51)Cr-release assays in vitro and by tumor bearing models in vivo. Our results demonstrated that the grp170-Pokemon chaperone complex could elicit T cell responses as determined by ELISPOT and (51)Cr-release assays. In addition, immunized C57BL/6 mice were challenged with subcutaneous (s.c.) injection of Lewis cancer cells to induce primary tumors. Treatment of mice with the grp170-Pokemon chaperone complex also significantly inhibited tumor growth and prolonged the life span of tumor-bearing mice. Our results indicated that the grp170-Pokemon chaperone complex might represent a powerful approach to tumor immunotherapy and have significant potential for clinical application. PMID:22317751

  7. Pathways towards an effective immunotherapy for Parkinson’s disease

    OpenAIRE

    Hutter-Saunders, Jessica AL; Mosley, Rodney Lee; Gendelman, Howard E.

    2011-01-01

    Immunizations that target specific types of immune responses are used commonly to prevent microbial infections. However, a range of immune responses may prove necessary to combat the ravages of neurodegenerative diseases. The goal is to eliminate the ‘root’ cause of neurodegenerative disorders, misfolded aggregated proteins, while harnessing adaptive immune responses to promote neural repair. However, immunization strategies used to elicit humoral immune responses against aberrant brain prote...

  8. Expert elicitation on the uncertainties associated with chronic wasting disease.

    Science.gov (United States)

    Tyshenko, Michael G; Oraby, Tamer; Darshan, Shalu; Westphal, Margit; Croteau, Maxine C; Aspinall, Willy; Elsaadany, Susie; Krewski, Daniel; Cashman, Neil

    2016-01-01

    A high degree of uncertainty exists for chronic wasting disease (CWD) transmission factors in farmed and wild cervids. Evaluating the factors is important as it helps to inform future risk management strategies. Expert opinion is often used to assist decision making in a number of health, science, and technology domains where data may be sparse or missing. Using the "Classical Model" of elicitation, a group of experts was asked to estimate the most likely values for several risk factors affecting CWD transmission. The formalized expert elicitation helped structure the issues and hence provide a rational basis for estimating some transmission risk factors for which evidence is lacking. Considered judgments regarding environmental transmission, latency of CWD transmission, management, and species barrier were provided by the experts. Uncertainties for many items were determined to be large, highlighting areas requiring more research. The elicited values may be used as surrogate values until research evidence becomes available. PMID:27556566

  9. Regret-based Reward Elicitation for Markov Decision Processes

    CERN Document Server

    Regan, Kevin

    2012-01-01

    The specification of aMarkov decision process (MDP) can be difficult. Reward function specification is especially problematic; in practice, it is often cognitively complex and time-consuming for users to precisely specify rewards. This work casts the problem of specifying rewards as one of preference elicitation and aims to minimize the degree of precision with which a reward function must be specified while still allowing optimal or near-optimal policies to be produced. We first discuss how robust policies can be computed for MDPs given only partial reward information using the minimax regret criterion. We then demonstrate how regret can be reduced by efficiently eliciting reward information using bound queries, using regret-reduction as a means for choosing suitable queries. Empirical results demonstrate that regret-based reward elicitation offers an effective way to produce near-optimal policies without resorting to the precise specification of the entire reward function.

  10. Increased Expression of miR-146a in Children With Allergic Rhinitis After Allergen-Specific Immunotherapy

    OpenAIRE

    LUO, XI; Hong, Haiyu; Tang, Jun; Wu, Xingmei; Lin, Zhibin; Ma, Renqiang; Fan, Yunping; Xu, Geng; Liu, Dabo; Li, Huabin

    2015-01-01

    Purpose MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Methods Twenty-four HDM-sensitized children with persistent AR...

  11. Less is more: lymphodepletion followed by hematopoietic stem cell transplant augments adoptive T-cell-based anti-tumor immunotherapy

    OpenAIRE

    Wrzesinski, Claudia; Restifo, Nicholas P

    2005-01-01

    Adoptive T-cell immunotherapy combined with non-myeloablative lymphodepletion has emerged as the most effective immunotherapy treatment for patients with metastatic melanoma (objective response rates of 50%). The mechanisms underlying this major advance in the field of immunotherapy include the elimination of regulatory elements and increased access to activating cytokines. This results in the activation of low-affinity T cells, enabling them to destroy tumors. We propose that a more complete...

  12. Preference Elicitation in Fully Probabilistic Design of Decision Strategies

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav; Guy, Tatiana Valentine

    Atlanta: IEEE, 2010, s. 5327-5332. ISBN 978-1-4244-7745-6. ISSN 0743-1546. [49th IEEE Conference on Decision and Control . Atlanta (US), 14.12.2010-18.12.2010] R&D Projects: GA ČR GA102/08/0567 Institutional research plan: CEZ:AV0Z10750506 Keywords : knowledge elicitation * Bayesian decision making * fullz probabilistic design Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2010/AS/karny-preference elicitation in fully probabilistic design of decision strategies.pdf

  13. Immunotherapy using dendritic cells and cytokine-induced killer for kidney cancer

    International Nuclear Information System (INIS)

    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)

  14. Belief elicitation in experiments: is there a hedging problem?

    Czech Academy of Sciences Publication Activity Database

    Blanco, M.; Engelmann, Dirk; Koch, A. K.; Normann, H.-T.

    2010-01-01

    Roč. 13, č. 4 (2010), s. 412-438. ISSN 1386-4157 Institutional research plan: CEZ:AV0Z70850503 Keywords : belief elicitation * hedging * experimental methodology Subject RIV: AH - Economics Impact factor: 1.868, year: 2010

  15. Eliciting Students' Beliefs about Who Is Good at Mathematics

    Science.gov (United States)

    Morge, Shelby P.

    2007-01-01

    This article highlights a series of activities designed to elicit students' mathematics-related beliefs, particularly those related to gender. As a result of the activities, females in upper-level classes rated themselves as having less confidence than males, and viewing a movie clip was sufficient for some students to modify their descriptions of…

  16. Expert Elicitation Method Selection Process and Method Comparison

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, Angela C.; Brothers, Alan J.; Walsh, Stephen J.; Whitney, Paul D.

    2010-09-21

    Research on integrative modeling has gained considerable attention in recent years and expert opinion has been increasingly recognized as an important data source and modeling contributor. However, little research has systematically compared and evaluated expert elicitation methods in terms of their ability to link to computational models that capture human behavior and social phenomena. In this paper, we describe a decision-making process we used for evaluating and selecting a task specific elicitation method within the framework of integrative computational social-behavioral modeling. From the existing literature, we identified the characteristics of problems that each candidate method is well suited to address. A small-scale expert elicitation was also conducted to evaluate the comparative strength and weaknesses of the methods against a number of consensus-based decision criteria. By developing a set of explicit method evaluation criteria and a description characterizing decision problems for the candidate methods, we seek to gain a better understanding of the feasibility and cost-effectiveness of integrating elicitation methods with computational modeling techniques. This serves an important first step toward expanding our research effort and trajectory toward greater interdisciplinary modeling research of human behavior.

  17. Computational Support for Early Elicitation and Classification of Tone

    Science.gov (United States)

    Bird, Steven; Lee, Haejoong

    2014-01-01

    Investigating a tone language involves careful transcription of tone on words and phrases. This is challenging when the phonological categories--the tones or melodies--have not been identified. Effects such as coarticulation, sandhi, and phrase-level prosody appear as obstacles to early elicitation and classification of tone. This article presents…

  18. The Role of Elicited Verbal Imitation in Toddlers' Word Learning

    Science.gov (United States)

    Hodges, Rosemary; Munro, Natalie; Baker, Elise; McGregor, Karla; Docking, Kimberley; Arciuli, Joanne

    2016-01-01

    This study is about the role of elicited verbal imitation in toddler word learning. Forty-eight toddlers were taught eight nonwords linked to referents. During training, they were asked to imitate the nonwords. Naming of the referents was tested at three intervals (one minute later [uncued], five minutes, and 1-7 days later [cued]) and recognition…

  19. Classifying groupware tools to improve communication in geographically distributed elicitation

    OpenAIRE

    Martín, Adriana; Martinez, Claudia; Martínez Carod, Nadina; Aranda, Gabriela N.; Cechich, Alejandra

    2003-01-01

    In a scene where stakeholders are geographically distributed, communication presents new challenges for research areas. Considering the characteristics of interpersonal communication and the virtual area where it is carried out, the importance of applying interdisciplinary approaches, such as Cognitive Engineering, is currently increasing. Particularly, our proposal aims at improving the interaction between stakeholders by applying learning models when eliciting distributed software requireme...

  20. Conditioned craving cues elicit an automatic approach tendency

    NARCIS (Netherlands)

    D. van Gucht; D. Vansteenwegen; O. Van den Bergh; T. Beckers

    2008-01-01

    In two experiments, we used a Pavlovian differential conditioning procedure to induce craving for chocolate. As a result of repeated pairing with chocolate intake, initially neutral cues came to elicit an automatic approach tendency in a speeded stimulus-response compatibility reaction time task. Th

  1. Creating a Framework: Art Therapy Elicits the Narrative

    Science.gov (United States)

    Harber, Karen

    2011-01-01

    A case study illustrates how art therapy was used to elicit the narrative of an adolescent male student in transition from incarceration to a transfer school setting. Childhood trauma was addressed in individual sessions and within a literacy group co-led by a reading specialist. The art therapist responded to the client's needs by broadening the…

  2. Elicitation of Pharmacologically Active Substances in Intact Medical Plant

    Czech Academy of Sciences Publication Activity Database

    Kužel, S.; Vydra, J.; Tříska, Jan; Vrchotová, Naděžda; Hrubý, Martin; Cígler, P.

    2009-01-01

    Roč. 57, č. 17 (2009), s. 7907-7911. ISSN 0021-8561 Institutional research plan: CEZ:AV0Z60870520; CEZ:AV0Z40500505 Keywords : elicitation * medical plant * Echinacea purpurea * secondary metabolite * foliar application * phenolics Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.469, year: 2009

  3. A Task that Elicits Reasoning: A Dual Analysis

    Science.gov (United States)

    Yankelewitz, Dina; Mueller, Mary; Maher, Carolyn A.

    2010-01-01

    This paper reports on the forms of reasoning elicited as fourth grade students in a suburban district and sixth grade students in an urban district worked on similar tasks involving reasoning with the use of Cuisenaire rods. Analysis of the two data sets shows similarities in the reasoning used by both groups of students on specific tasks, and the…

  4. Structured Language Requirement Elicitation Using Case Base Reasoning

    Directory of Open Access Journals (Sweden)

    Marryam Murtaza

    2013-12-01

    Full Text Available Requirement elicitation is very difficult process in highly challenging and business based software as well as in real time software. Common problems associated with these types of software are rapidly changing the requirements and understanding the language of the layman person. In this study, a framework for requirement elicitation by using knowledge based system is proposed, which is very helpful for knowledge documentation, intelligent decision support, self-learning and more specifically it is very helpful for case based reasoning and explanation. Basically in this method requirements are gathered from Artificial Intelligence (AI expert system from various sources e.g., via interviews, scenarios or use cases. Then, these are converted into structured natural language using ontology and this new problem/case is put forward to Case Based Reasoning (CBR. CBR based on its previous information having similar requirements combines with new case and suggests a proposed solution. Based on this solution a prototype is developed and delivered to customer. The use of case-based reasoning in requirements elicitation process has greatly reduced the burden and saved time of requirement analyst and results in an effective solution for handling complex or vague requirements during the elicitation process.

  5. Novel Antibody-Based Proteins for Cancer Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fuenmayor, Jaheli; Montaño, Ramon F., E-mail: jfuenmay@ivic.gob.ve [Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas. Caracas, 1020-A (Venezuela, Bolivarian Republic of)

    2011-08-19

    The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.

  6. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    Directory of Open Access Journals (Sweden)

    David Escors

    2013-07-01

    Full Text Available The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(g-retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and b-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

  7. Novel Antibody-Based Proteins for Cancer Immunotherapy

    International Nuclear Information System (INIS)

    The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future

  8. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    International Nuclear Information System (INIS)

    The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells

  9. Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer.

    Science.gov (United States)

    Lamm, D L; Thor, D E; Harris, S C; Reyna, J A; Stogdill, V D; Radwin, H M

    1980-07-01

    Thirty-seven patients were enrolled in a randomized prospective study to compare standard surgical therapy for superficial bladder cancer to standard therapy plus bacillus Calmette-Guerin (BCG). Side effects of BCG have been tolerated well and include dysuria in 95 per cent of the patients, urinary frequency in 83 per cent, hematuria in 39 per cent, fever in 22 per cent and nausea in 22 per cent. Of 19 control patients 8 (42 per cent) had recurrent tumors in the followup period, compared to 3 of 18 patients (17 per cent) treated with BCG. One patient treated wih BCG had 2 recurrences, yielding a recurrence rate of 22 per cent in the group receiving BCG compared to 42 per cent in controls. When the incidence of recurrent tumors in matched intervals before and after entry into the protocol is compared, no change in the rate of tumor recurrence (p equals 0.726 chi-square) occurred in controls, whereas tumor recurrences were reduced significantly in the group treated with BCG (p equals 0.010 chi-square). The reduction in tumor recurrence in patients treated with BCG compared to controls is statistically significant (p equals 0.029 chi-square). Of 4 patients who presented with new bladder tumors remain free of tumor after BCG therapy, while 2 of 5 comparable control patients developed recurrent tumors. Intravesical and percutaneous BCG immunotherapy appears to decrease the rate of tumor recurrence in patients followed for 1 year. PMID:6997513

  10. Mucosal immunization application to allergic disease: sublingual immunotherapy.

    Science.gov (United States)

    Frati, Franco; Moingeon, Philippe; Marcucci, Francesco; Puccinelli, Paola; Sensi, Laura; Di Cara, Giuseppe; Incorvaia, Cristoforo

    2007-01-01

    Sublingual immunotherapy (SLIT) is an effective and safe treatment for respiratory allergy, and its mechanism of action currently is investigated with increasing attention. Studies of pharmacokinetics showed that allergen extracts administered via the sublingual route are not directly absorbed by the oral mucosa but are long retained at mucosal level, where the allergen molecules are captured by dendritic cells and, following their migration in the draining lymph nodes, presented to T cells. This seems to be the pivotal factor underlying the mechanisms of action of SLIT, at least for the long-term effects, and for the short-term efficacy, observed with ultrarush or coseasonal treatment, a down-regulation of mast cells resulting in hyporeactivity at the peak of the pollen season may be suggested. Regarding the clinically established long-lasting effects, the core mechanism is likely to consist of T regulatory (Treg) cell activation. In particular, Treg cells differentiate from naive T cells after application of soluble antigens to the mucosae, a crucial factor being the tolerogenic function of dendritic cells, and exert a suppressive effect on both Th1 and Th2 responses. Moreover, at least for the type 1 cells (Treg1), a production of IL-10 with consequent down-modulation of the immune response has been reported. Another characteristic of sublingual immunization is the absence of effectors cells, viz., mast cells, basophils, and eosinophils, in the oral mucosa of allergic subjects, which account for the excellent tolerability of SLIT. PMID:17390755

  11. Assays for predicting and monitoring responses to lung cancer immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Cristina Teixid; Niki Karachaliou; Maria Gonzlez-Cao; Daniela Morales-Espinosa; Rafael Rosell

    2015-01-01

    AbstrAct Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 (PD-1) and its ligand (PD-L1), have recently emerged as important targets. hTe interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor effcacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer (NSCLC). Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. hTerefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry (IHC) with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack speciifcity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-1/PD-L1 pathway.

  12. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    Energy Technology Data Exchange (ETDEWEB)

    Liechtenstein, Therese, E-mail: t.liechtenstein.12@ucl.ac.uk [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Perez-Janices, Noemi; Escors, David [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Navarrabiomed Fundacion Miguel Servet, 3 Irunlarrea St., Hospital Complex of Navarra, 31008 Pamplona, Navarra (Spain)

    2013-07-02

    The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

  13. Combination of photodynamic therapy and immunotherapy - evolving role in dermatology

    Science.gov (United States)

    Wang, Xiu-Li; Wang, Hong-Wei; Huang, Zheng

    2008-02-01

    Photodynamic therapy (PDT) is a promising treatment modality. It offers alternative options in the treatment of cancer and vascular diseases. In cancer treatment, PDT has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. More recently, its application has also been expanded to solid tumors. However, its antitumor efficacy remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the primary local cytotoxicity, PDT might induce secondary host immune responses, which may further enhance PDT's therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced local and systemic antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, PDT's antitumor efficacy might also be enhanced through an effective immunoadjuvant or immunomodulator. Our recent clinical data also indicate that improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy for the treatment of pre-malignant skin diseases. For instance, the combination of topical ALA-PDT and Imiquimod is effective for the treatment of genital bowenoid papulosis. This presentation will also report our preliminary data in developing combination approaches of PDT and immunotherapy for actinic keratosis (AK), basal cell carcinomas (BCCs) and Bowen's disease.

  14. Interleukin-33 in tumorigenesis, tumor immune evasion, and cancer immunotherapy.

    Science.gov (United States)

    Lu, Binfeng; Yang, Min; Wang, Qingqing

    2016-05-01

    Interleukin-33 (IL-33) is a member of the IL-1 gene family and mainly expressed in the nucleus of tissue lining cells, stromal cells, and activated myeloid cells. IL-33 is considered a damage-associated molecular pattern (DAMP) molecule and plays an important role in many physiological and pathological settings such as tissue repair, allergy, autoimmune disease, infectious disease, and cancer. The biological functions of IL-33 include maintaining tissue homeostasis, enhancing type 1 and 2 cellular immune responses, and mediating fibrosis during chronic inflammation. IL-33 exerts diverse functions through signaling via its receptor ST2, which is expressed in many types of cells including regulatory T cells (Treg), group 2 innate lymphoid cells (ILC2s), myeloid cells, cytotoxic NK cells, Th2 cells, Th1 cells, and CD8(+) T cells. Tumor development results in downregulation of IL-33 in epithelial cells but upregulation of IL-33 in the tumor stroma and serum. The current data suggest that IL-33 expression in tumor cells increases immunogenicity and promotes type 1 antitumor immune responses through CD8(+) T cells and NK cells, whereas IL-33 in tumor stroma and serum facilitates immune suppression via Treg and myeloid-derived suppressor cell (MDSC). Understanding the role of IL-33 in cancer immunobiology sheds lights on targeting this cytokine for cancer immunotherapy. PMID:26922618

  15. Immunotherapy for Alzheimer’s Disease: Past, Present and Future

    Directory of Open Access Journals (Sweden)

    Brian Spencer

    2014-06-01

    Full Text Available Alzheimer’s disease (AD is an incurable, progressive, neurodegenerative disorder affecting over 5 million people in the US alone. This neurological disorder is characterized by widespread neurodegeneration throughout the association cortex and limbic system caused by deposition of Aβ resulting in the formation of plaques and tau resulting in the formation of neurofibrillary tangles. Active immunization for Aß showed promise in animal models of Alzheimer’s disease; however, the models were unable to predict the off-target immune effects in human patients. A few patients in the initial trial suffered cerebral meningoencephalitis. Recently, passive immunization has shown promise in the lab with less chance of off-target immune effects. Several trials have attempted using passive immunization for Aß, but again, positive end points have been elusive. The next generation of immunotherapy for Alzheimer’s disease may involve the marriage of anti-Aß antibodies with technology aimed at improving transport across the blood-brain barrier. Receptor mediated transport of antibodies may increase CNS exposure and improve the therapeutic index in the clinic.

  16. Assays for predicting and monitoring responses to lung cancer immunotherapy

    International Nuclear Information System (INIS)

    Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 (PD-1) and its ligand (PD-L1), have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer (NSCLC). Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry (IHC) with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-1/PD-L1 pathway

  17. Allergen immunotherapy with nanoparticles containing lipopolysaccharide from Brucella ovis.

    Science.gov (United States)

    Gómez, Sara; Gamazo, Carlos; San Roman, Beatriz; Ferrer, Marta; Sanz, Maria Luisa; Espuelas, Socorro; Irache, Juan M

    2008-11-01

    The adjuvant and protective capacity against anaphylactic shock of the association between rough lipopolysaccharide of Brucella ovis (LPS) coencapsulated with ovalbumin (OVA), as a model allergen, in Gantrez AN nanoparticles was investigated. Several strategies were performed in order to study the adjuvant effect of the LPS either encapsulated or coating the nanoparticles. OVA, as well as LPS, was incorporated either during the manufacturing process (OVA-encapsulated or LPS-encapsulated nanoparticles, respectively) or after the preparation (OVA-coated or LPS-coated nanoparticles, respectively). After the administration of 10 microg of OVA incorporated in the different formulations, all the nanoparticles, with or without LPS, were capable of amplifying the immune response (IgG(1) and IgG(2a)). However, in a model of sensitized mice to OVA, the formulation with OVA and LPS-entrapped inside the nanoparticles administered intradermally in three doses of 3 microg of OVA each was the only treatment that totally protected the mice from death after a challenge with an intraperitoneal injection of OVA. In contrast, the control group administered with OVA adsorbed onto a commercial alhydrogel adjuvant showed 80% mortality. These results are highly suggestive for the valuable use of Gantrez nanoparticles combined with rough LPS of B. ovis in immunotherapy. PMID:18582571

  18. Immunotherapy of melanoma: present options and future promises.

    Science.gov (United States)

    Rotte, Anand; Bhandaru, Madhuri; Zhou, Youwen; McElwee, Kevin J

    2015-03-01

    Metastatic melanoma is notorious for its immune evasion and resistance to conventional chemotherapy. The recent success of ipilimumab, a human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), in increasing the median survival time and stabilizing the disease progression renewed, hopes in treatment for melanoma. Currently, ipilimumab and high-dose interleukin-2 (IL-2; Aldesleukin) are approved as monotherapies for the treatment of patients with unresectable advanced melanoma, and pegylated interferon-α2b (p-IFN-α2b) is approved as an adjuvant for the treatment of patients with surgically resected high-risk melanoma. The present review describes the currently approved immune-modulators and the promising immune-based interventions that are currently in clinical trials. We present the four commonly used strategies to boost immune responses against the tumors; monoclonal antibodies, cytokines, cancer vaccines, and adoptive T cell transfer. The corresponding lists of ongoing clinical trials include details of the trial phase, target patients, intervention details, status of the study, and expected date of completion. Further, our review discusses the challenges faced by immunotherapy and the various strategies adopted to overcome them. PMID:25589384

  19. Potential biomarker for checkpoint blockade immunotherapy and treatment strategy.

    Science.gov (United States)

    Dong, Zhong-Yi; Wu, Si-Pei; Liao, Ri-Qiang; Huang, Shu-Mei; Wu, Yi-Long

    2016-04-01

    Programmed cell death protein-1 (PD-1) and ligand (PD-L1) provide an important escape mechanism from immune attack, and blockade therapy of these proteins show promising clinical benefits in many types of cancer. PD-L1 can be induced by interferon-gamma (IFN-γ), hypoxia, or toll-like receptor (TLR)-mediated pathways that confer adaptive immune resistance, or upregulated by oncogenic signals leading to constitutive expression and resulting in intrinsic immune resistance. The PD-1/PD-L1 checkpoint blockade, which targets regulatory pathways in T cells to overcome immune resistance, is correlated to PD-L1 expression pattern and the presence of tumor-infiltrating lymphocytes (TILs). Meanwhile, immunogenic mutation loads show significant response to checkpoint blockade, which is probably due to PD-1/L1 status and TIL content. Finally, the clinical strategies to design effective checkpoint-targeting immunotherapies are based on the classification of inducible/constitutive expression of PD-L1 and the presence of TILs. PMID:26779629

  20. Single-Chain Fragment Variable Passive Immunotherapies for Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Liang Huang

    2013-09-01

    Full Text Available Accumulation of misfolded proteins has been implicated in a variety of neurodegenerative diseases including prion diseases, Alzheimer’s disease (AD, Parkinson’s disease (PD, and Huntington’s disease (HD. In the past decade, single-chain fragment variable (scFv -based immunotherapies have been developed to target abnormal proteins or various forms of protein aggregates including Aβ, SNCA, Htt, and PrP proteins. The scFvs are produced by fusing the variable regions of the antibody heavy and light chains, creating a much smaller protein with unaltered specificity. Because of its small size and relative ease of production, scFvs are promising diagnostic and therapeutic reagents for protein misfolded diseases. Studies have demonstrated the efficacy and safety of scFvs in preventing amyloid protein aggregation in preclinical models. Herein, we discuss recent developments of these immunotherapeutics. We review efforts of our group and others using scFv in neurodegenerative disease models. We illustrate the advantages of scFvs, including engineering to enhance misfolded conformer specificity and subcellular targeting to optimize therapeutic action.

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

    International Nuclear Information System (INIS)

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

  2. Clinical effects of laser immunotherapy on metastatic cancer patients

    Science.gov (United States)

    Naylor, Mark F.; Lam, Anh K.; Bahavar, Cody F.; Nordquist, Robert E.; Chen, Wei R.

    2016-03-01

    Clinical trials of late-stage breast cancer patients and late-stage melanoma patients treated by laser immunotherapy (LIT) have shown promising results. In a 2010 study of Li et al, eleven late-stage melanoma patients received LIT in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. Long-term, positive response was observed in six patients. All lesions in the treatment area of the patients responded to LIT, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%.2 In 2011, Li et al, treated ten late stage breast cancer patients with LIT.1 In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%.1 This review demonstrates that LIT is safe and well tolerated, so it can be easily applied on an outpatient basis and can be combined with other pharmaceutical modalities to improve the therapeutic response of metastatic cancers.

  3. Neoadjuvant immunotherapy enhances radiosensitivity through natural killer cell activation.

    Science.gov (United States)

    Chi, Chau-Hwa; Wang, Yu-Shan; Yang, Chieh-Han; Chi, Kwan-Hwa

    2010-02-01

    We investigated whether natural killer (NK) cells in the tumor microenvironment have a radiosensitization effect. The radiosensitization effect of combined CpG and Herceptin((R)) (Genentech, Inc., South San Francisco, CA) (CpG/Herceptin), given before or after radiation, was evaluated by using a murine colon cancer cell line overexpressing human HER2/neu, CT26HER2/neu. In vitro radiosensitization effects were investigated by coculture of CT26HER2/neu with splenocytes, CpG, and Herceptin before applying radiation. Tumor cells, cocultured with CpG-pretreated splenocytes and Herceptin, were more vulnerable to radiation damage. In BALB/c mice injected with CT26HER2/neu, CpG/Herceptin administered before radiotherapy was associated with a better retardation of tumor growth than when administered after radiotherapy. The radiosensitization effect was significantly abrogated by NK-cell depletion, indicating that NK cells play an essential role in it. Further, surviving mice treated with CpG or CpG/Herceptin and reverse transcriptase were resistant to renewed tumor challenge, suggesting the presence of an induced immune response to the tumor. Neoadjuvant immunotherapy with CpG/Herceptin may improve response to radiotherapy of HER2/neu-expressing tumors. PMID:20187795

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-22

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

  6. Immunotherapy using algal-produced Ara h 1 core domain suppresses peanut allergy in mice.

    Science.gov (United States)

    Gregory, James A; Shepley-McTaggart, Ariel; Umpierrez, Michelle; Hurlburt, Barry K; Maleki, Soheila J; Sampson, Hugh A; Mayfield, Stephen P; Berin, M Cecilia

    2016-07-01

    Peanut allergy is an IgE-mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen-specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h 1 and Ara h 2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal-produced Ara h 1 core domain and Ara h 2 have a reduced affinity for IgE from peanut-allergic patients. We further found that immunotherapy using algal-produced Ara h 1 core domain confers protection from peanut-induced anaphylaxis in a murine model of peanut allergy. PMID:26801740

  7. A case of malignant melanoma of the maxilla treated by adoptive immunotherapy after fast neutron therapy

    International Nuclear Information System (INIS)

    A 77-year-old male patient with malignant melanoma was treated by fast neutron therapy and immunotherapy. Total dose of fast neutron applied to the primary lesion was 1905 cGy per 21 fractionation for 46 days. For adoptive immunotherapy, lymphocytes were collected from the peripheral blood drawn from the patient 2 days after the injection of cyclophosphamide. T cells were further purified by passing the lymphocytes through nylon wool. Cytotoxic T cells were induced by incubating the T cells mixed with allogeneic malignant melanoma cells and a small number of patient's adherent cells, and activated with recombinant interleukin-2 (γ IL-2). Our patient and the patient from whom stimulating melanoma cells were derived shared A locous 24 and B locous 51 of MHC class I antigens in common. Thus prepared cytotoxic T cells were inoculated to the patient via the maxillary artery, 3 to 4 times a week for one month. Total amount of cells transferred was 5.6 x 108 (97% lymphocytes). Primary lesion reduced markedly by the therapies. During adoptive immunotherapy, increase in natural killer cells and decrease in both suppressor/inducer T-cells and macrophages were observed. However, lung metastases appeared 3 months after adoptive immunotherapy. While the nonspecific immunotherapy (OK-432 injection) was being conducted thereafter, growth of the metastatic lesions of the lung was kept gentle but became obvious after the suspension of the treatment. (author)

  8. LYMPHOCYTE PHENOTYPE IN PATIENTS WITH SKIN MELANOMA AFTER IMMUNOTHERAPY OF ACTIVATED LYMPHOCYTES

    Directory of Open Access Journals (Sweden)

    E. V. Abakushina

    2015-01-01

    Full Text Available The major medical problem in the treatment of skin melanoma is improvement methods of treatment, increasing their effectiveness and safety. In this study, adoptive immunotherapy, using lymphocytes activated in vitro, was performed in 15 patients with metastatic melanoma. Evaluated the phenotype of peripheral blood lymphocytes and activation markers (HLA-DR, CD25, CD314, CD38, CD69 before and 3-4 weeks after immunotherapy. It is shown that for these patients is characterized by increasing the number of CD25+ and Treg lymphocytes in the bloodstream, which has not changed after immunotherapy. Adoptive immunotherapy in combination with chemotherapy resulted in a decrease of absolute number of lymphocyte, B- and T-lymphocytes, T helper cells, NKT-cells, CD314+ lymphocytes, CD38+ lymphocytes and immature T-lymphocytes (CD3+CD38+ (р < 0,05. However, there was a positive dynamic to increase the percentage of NK-cells to 32% and CD69+NK-cells to 21% and significant increase in expression of HLA-DR on all lymphocytes (p < 0.05. Adoptive immunotherapy characterized by the absence of side effects and can be recommended as accompanying to basic radiation and chemotherapy.

  9. Peptide-based allergen specific immunotherapy for the treatment of allergic disorders.

    Science.gov (United States)

    El-Qutob, David; Reche, Pedro; Subiza, José L; Fernández-Caldas, Enrique

    2015-01-01

    Allergen specific immunotherapy (ASIT) and environmental control are the only etiologic treatments of allergic rhino-conjunctivitis, asthma and atopic dermatitis. The clinical benefit of ASIT relies on the selection of the patients and the identification and administration of the allergen, or allergens. Different routes of administration have been investigated, including subcutaneous, intradermal, epicutaneous, sublingual, inhaled, or intra-lymphatic. While subcutaneous and sublingual allergen specific immunotherapy may require from 3 to 5 years of treatment, clinical efficacy with intra-lymphatic treatment can be achieved after 3 injections. The most severe side effect of ASIT is anaphylaxis. Novel approaches are being investigated to reduce the allergenicity of immunotherapy vaccines, maintaining immunogenicity. Peptide immunotherapy has been directed mostly against autoimmune diseases, but the use of synthetic peptides for ASIT is a promising field in basic science, applied immunology and in clinical development. Short synthetic peptides bear allergen-specific CD4 T-cell epitopes which induce tolerance by stimulating regulatory (Treg) and Th1 cells. In the present patent review, we describe new trends in allergen immunotherapy using peptides, which, from a clinical point of view, are promising. PMID:25760734

  10. P53-specific T cell responses in patients with malignant and benign ovarian tumors : Implications for p53 based immunotherapy

    NARCIS (Netherlands)

    Lambeck, Annechien; Leffers, Ninke; Hoogeboom, Baukje-Nynke; Sluiter, Wim; Hamming, Ineke; Klip, Harry; ten Hoor, Klaske; Esajas, Martha; van Oven, Magda; Drijfhout, Jan-Wouter; Platteel, Inge; Offringa, Rienk; Hollema, Harry; Melief, Kees; van der Burg, Sjoerd; van der Zee, Ate; Daemen, Toos; Nijman, Hans

    2007-01-01

    Despite intensive treatment, 70% of the ovarian cancer patients will develop recurrent disease, emphasizing the need for new approaches such as immunotherapy. A promising antigenic target for immunotherapy in ovarian cancer is the frequently overexpressed p53 protein. The aim of the study was to eva

  11. Galectin-1 drives lymphoma CD20 immunotherapy resistance: validation of a preclinical system to identify resistance mechanisms.

    Science.gov (United States)

    Lykken, Jacquelyn M; Horikawa, Mayuka; Minard-Colin, Veronique; Kamata, Masahiro; Miyagaki, Tomomitsu; Poe, Jonathan C; Tedder, Thomas F

    2016-04-14

    Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal-1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy. PMID:26888257

  12. Dendritic cell-based immunotherapy induces transient clinical response in advanced rat fibrosarcoma - comparison with preventive anti-tumour vaccination

    Czech Academy of Sciences Publication Activity Database

    Kučera, A.; Pýcha, K.; Pajer, Petr; Špíšek, R.; Škába, R.

    2009-01-01

    Roč. 55, č. 4 (2009), s. 119-125. ISSN 0015-5500 Institutional research plan: CEZ:AV0Z50520514 Keywords : dendritic cells * immunotherapy * cancer immunotherapy * chemotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2009

  13. Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care : study design and recruitment

    NARCIS (Netherlands)

    de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roder, Esther; de Groot, Hans; de Jongste, Johan C.; van Wijk, Roy Gerth; van der Wouden, Johannes C.

    2008-01-01

    Background: For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized doub

  14. ALLERGEN-SPECIFIC IMMUNOTHERAPY: VACCINES FOR ALLERGIC DISEASES

    Directory of Open Access Journals (Sweden)

    A. S. Fedorov

    2015-10-01

    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

  15. Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

    International Nuclear Information System (INIS)

    Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies

  16. Mechanistic insights into the oncolytic activity of vesicular stomatitis virus in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Simovic B

    2015-10-01

    Full Text Available Boris Simovic, Scott R Walsh, Yonghong Wan Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada Abstract: Immunotherapy and oncolytic virotherapy have both shown anticancer efficacy in the clinic as monotherapies but the greatest promise lies in therapies that combine these approaches. Vesicular stomatitis virus is a prominent oncolytic virus with several features that promise synergy between oncolytic virotherapy and immunotherapy. This review will address the cytotoxicity of vesicular stomatitis virus in transformed cells and what this means for antitumor immunity and the virus' immunogenicity, as well as how it facilitates the breaking of tolerance within the tumor, and finally, we will outline how these features can be incorporated into the rational design of new treatment strategies in combination with immunotherapy. Keywords: virotherapy, rhabdovirus, anti-tumor immunity, t cell, natural killer cell, therapeutic vaccine

  17. Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, Jo A.; Jochems, Caroline [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Gulley, James L. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Schlom, Jeffrey, E-mail: js141c@nih.gov; Tsang, Kwong Y. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2012-12-11

    Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies.

  18. Adoptive immunotherapy combined chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.

    Science.gov (United States)

    Qian, Haili; Wang, Haijuan; Guan, Xiuwen; Yi, Zongbi; Ma, Fei

    2016-06-01

    The aim of this study was to compare the efficacies between adoptive immunotherapy combined chemoradiotherapy and chemoradiotherapy alone in patients with non-small-cell lung cancer (NSCLC). The databases PubMed, EMBASE, and Cochrane database were searched to identify eligible clinical trials. Data analyses were carried out using a comprehensive meta-analysis program, version 2 software. A total of seven articles were finally included in the analysis. Meta-analyses showed that compared with chemoradiotherapy alone, adoptive immunotherapy combined with chemoradiotherapy could improve the 2-year overall survival [odds ratio (OR)=2.45, 95% confidence interval (CI): 1.60-3.75, Pshiver, nausea, fatigue, etc. and severe toxicities were not observed. Adoptive immunotherapy combined with chemoradiotherapy can delay the recurrence of NSCLC and improve survival in patients, where the benefits are even more significant in patients with early-stage NSCLC. PMID:26872311

  19. DNA-based immunotherapy for HPV-associated head and neck cancer.

    Science.gov (United States)

    Aggarwal, Charu

    2016-10-01

    Squamous cell carcinoma of the head and neck (SCCHN) accounts for 3% of all cancers. Most patients present with locally advanced disease, where multimodality therapies are used with curative intent. Despite favorable early local treatment results, about one third of the patients will eventually develop metastatic disease. Immunotherapy offers a novel therapeutic strategy beyond cytotoxic chemotherapy, with initial approvals in melanoma and non-small-cell lung cancer. HPV-associated SCCHN is a distinct subset, with unique epidemiology and treatment outcomes. Both subsets of SCCHN (HPV-related or not) are particularly favorable for immunotherapy, as immune evasion and dysregulation have been shown to play a key role in the initiation and progression of disease. This review focuses on the latest developments in immunotherapy in SCCHN, with a particular focus on DNA-based approaches including vaccine and adoptive cellular therapies. PMID:27605067

  20. Immunotherapy for genitourinary cancer: state of the art and new perspectives.

    Science.gov (United States)

    Cattrini, Carlo; Dellepiane, Chiara; Cavo, Alessia; Buzzatti, Giulia; Tolomeo, Francesco; Messina, Carlo; Boccardo, Francesco

    2016-08-01

    In the last few years, cancer immunotherapy has changed the natural history and treatment strategies of a number of solid tumors, including melanoma and lung cancer. The anti-PD-1 nivolumab showed a survival benefit compared with everolimus in the second-line treatment of renal cell carcinoma, resulting in a radical shift in perspective in the treatment of this neoplasia and suggesting a new scenario beyond tyrosine kinase inhibitors. Checkpoint inhibitors might also improve the treatment of urothelial cancer, considering the promising results achieved so far and the relatively low efficacy of currently available treatments. Sipuleucel-T was the first approved immunotherapy for prostate cancer, showing a clear benefit in overall survival, and paved the way for the clinical testing of other novel cancer vaccines. This review provides a comprehensive overview of the current knowledge and new perspectives of immunotherapy in the treatment of urogenital malignancies. PMID:27183027

  1. Use of new technology to improve utilization and adherence to immunotherapy.

    Science.gov (United States)

    Joshi, Smita; Dimov, Ves

    2014-01-01

    Technology and social media have dramatically altered the landscape in which we practice medicine. Clinicians have increasingly turned to technology and the internet to enhance patient care. Allergists have used these modalities to improve utilization and adherence to immunotherapy. Electronic medical records (EMRs) are being widely adopted by allergy practices and some offer allergy/immunology specific modules that aid in daily workflow. The development of specialized devices that reduce pain associated with immunotherapy administration may improve compliance with immunotherapy. Social media and other forms of electronic communication such as e-mail, Facebook, Twitter, short message service (SMS), and YouTube give clinicians multiple avenues to disseminate information and reach their patients, possibly improving patient adherence to therapy. Finally, tablet computers, online networks, and electronic surveys provide additional ways to connect patients and physicians. PMID:25709743

  2. Induced pluripotent stem cells: Challenges and opportunities for cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Patty eSachamitr

    2014-04-01

    Full Text Available Despite recent advances in cancer treatment over the past 30 years, therapeutic options remain limited and do not always offer a cure for malignancy. Given that tumour associated antigens (TAA are, by definition, self-proteins, the need to productively engage autoreactive T cells remains at the heart of strategies for cancer immunotherapy. These have traditionally focussed on the administration of autologous monocyte-derived dendritic cells (moDC pulsed with TAA, or the ex vivo expansion and adoptive transfer of tumour infiltrating lymphocytes (TIL as a source of TAA-specific cytotoxic T cells (CTL. Although such approaches have shown some efficacy, success has been limited by the poor capacity of moDC to cross-present exogenous TAA to the CD8+ T cell repertoire and the potential for exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer opportunities to generate patient-specific stem cell lines with the potential to differentiate in vitro into cell types whose properties may help address these issues. Here we review recent success in the differentiation of NK cells from human induced pluripotent stem (iPS cells as well as minor subsets of DC with therapeutic potential, including CD141+XCR1+ DC, capable of cross-presenting TAA to naïve CD8+ T cells. Furthermore, we review recent progress in the use of TIL as the starting material for the derivation of iPSC lines, thereby capturing their antigen specificity in a self-renewing stem cell line, from which potentially unlimited numbers of naïve TAA-specific T cells may be differentiated, free of the risks of exhaustion.

  3. 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. PMID:15585110

  4. Improving the safety of oral immunotherapy for food allergy.

    Science.gov (United States)

    Vazquez-Ortiz, Marta; Turner, Paul J

    2016-03-01

    Food allergy is a major public health problem in children, impacting upon the affected individual, their families and others charged with their care, for example educational establishments, and the food industry. In contrast to most other paediatric diseases, there is no established cure: current management is based upon dietary avoidance and the provision of rescue medication in the event of accidental reactions, which are common. This strategy has significant limitations and impacts adversely on health-related quality of life. In the last decade, research into disease-modifying treatments for food allergy has emerged, predominantly for peanut, egg and cow's milk. Most studies have used the oral route (oral immunotherapy, OIT), in which increasing amounts of allergen are given over weeks-months. OIT has proven effective to induce immune modulation and 'desensitization' - that is, an increase in the amount of food allergen that can be consumed, so long as regular (typically daily) doses are continued. However, its ability to induce permanent tolerance once ongoing exposure has stopped seems limited. Additionally, the short- and long-term safety of OIT is often poorly reported, raising concerns about its implementation in routine practice. Most patients experience allergic reactions and, although generally mild, severe reactions have occurred. Long-term adherence is unclear, which rises concerns given the low rates of long-term tolerance induction. Current research focuses on improving current limitations, especially safety. Strategies include alternative routes (sublingual, epicutaneous), modified hypoallergenic products and adjuvants (anti-IgE, pre-/probiotics). Biomarkers of safe/successful OIT are also under investigation. PMID:26593873

  5. Congruence between international guidelines and mite specific immunotherapy prescribing practices.

    Science.gov (United States)

    Antonicelli, L; Braschi, M C; Bilò, M B; Angino, A; Pala, A P; Baldacci, S; Maio, S; Bonifazi, F

    2011-10-01

    Both rhinitis (ARIA) and asthma (GINA) guidelines recommend allergen-specific immunotherapy (SIT) tailored to the specific levels of severity of each disease. Real world studies evaluating congruence between these recommendations and prescribing practice in the single patient with comorbidity are lacking. An observational polycentric study was carried out in 518 patients recruited from 34 allergy centers throughout Italy. A questionnaire was administered to each consecutive patient over a span of four months. Taking into account guideline recommendations for both diseases, concomitant in the same patient, three subsets resulted: patients not eligible for SIT (11%); patients eligible for SIT for one disease only (60%); patients eligible for SIT for both diseases (29%). SIT was prescribed in 257 (49.6%) subjects. The level of SIT prescription was about 50% in all three groups. Consistent with the ARIA guidelines, a correlation between the prescription of SIT and the severity of rhinitis was documented (r=0.87; p=0.001). An association with asthma severity was found (p=0.02), but the trend was inconsistent with the GINA recommendations. Young age was the most important factor for SIT prescription both in the eligible for one disease and in the eligible for both diseases subset. The tendency towards worsening of symptoms was a factor for SIT in the eligible for one disease subset. In mite allergic patients with rhinitis and asthma comorbidity, the severity of rhinitis and the young age are the most important factors driving the SIT prescription. The congruence of SIT prescription was better for the ARIA than GINA guidelines. PMID:21628094

  6. CD22 as a target of passive immunotherapy.

    Science.gov (United States)

    Cesano, Alessandra; Gayko, Urte

    2003-04-01

    CD22 is a 135-kd B-cell restricted sialoglycoprotein present in the cytoplasm of virtually all B-lineage cells but expressed on the B-cell surface only at mature stages of differentiation. In humans, the vast majority of IgM(+)IgD(+) B cells express cell-surface CD22, while in lymphoid tissues CD22 expression is high in follicular mantle and marginal zone B cells and weak in germinal center B cells. In B-cell malignancies, CD22 expression ranges from 60% to 80% depending on the histological type and on the assays used. The function of the CD22 molecule is uncertain, although recent studies have suggested roles for the molecule both as a component of the B-cell activation complex and as an adhesion molecule. CD22-deficient mice have a reduced number of mature B cells in the bone marrow and circulation; the B cells have a shorter lifespan and enhanced apoptosis, thus indicating a key role of this antigen in B-cell development/survival. After binding with its natural ligand(s) or antibodies, CD22 is rapidly internalized; this provides a potent costimulatory signal in primary B-cell and proapoptotic signals in neoplastic B cells. Preclinically CD22 has been shown to be an effective target for immunotherapy of B-cell malignancies using either "naked" or toxin-labeled or radiolabeled monoclonal antibodies. Clinical trials in patients with non-Hodgkin's lymphoma (NHL) (both indolent and aggressive disease) are now ongoing with a humanized naked anti-CD22 antibody (epratuzumab, Amgen Inc, thousand Oaks, CA and Immunomedics Inc, Morris Plains, NJ) used as single agent or in combination with other monclonal antibodies (ie, rituximab) and/or chemotherapy. Preliminary data from these studies showed these approaches to be effective and well-tolerated. PMID:12720147

  7. Update on benefit of immunotherapy and targeted therapy in melanoma: the changing landscape

    Directory of Open Access Journals (Sweden)

    Srivastava N

    2014-06-01

    Full Text Available Neeharika Srivastava, David McDermott Department of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Malignant melanoma is on the rise. There have been recent advances in targeted agents and immunotherapies that have improved the management and treatment of patients with advanced melanoma. This review discusses the clinical efficacy and unique side effects of targeted immunotherapy and the role of predictive biomarkers in better selection of patients who would derive most benefit from specific treatments. Additionally, this review addresses concerns about the best sequencing algorithms for the currently available targeted agents. By thoroughly and extensively researching through PubMed and the American Society of Clinical Oncology, 69 published articles and abstracts were identified as addressing topics related to malignant melanoma and immunotherapy. The research was divided into subcategories discussing cytokine-based therapy, immunotherapy, molecularly targeted agents, other novel targeted agents, and combination regimens for malignant melanoma. New immune checkpoint inhibitors and targeted agents are able to improve immune-mediated regulatory effects against tumors and, specifically in advanced melanoma, are associated with improvement in overall survival. These new agents have distinct side effects that are often controlled and reversed with dose reductions and/or use of corticosteroids. Currently, there are clinical trials underway to assess the role of combination therapy, whereas other trials are focusing on devising algorithms to delineate how best to sequentially administer these drugs. Although there has been tremendous progress in the management of advanced melanoma with immunotherapy and targeted agents, there is still much to be learned about clinically useful predictive biomarkers and combination therapies as well as how to administer these agents safely. Keywords: melanoma, immunotherapy

  8. The use of photo-elicitation in field research

    Directory of Open Access Journals (Sweden)

    Elisa Bignante

    2010-02-01

    Full Text Available This paper examines the use of visual methods in geographical field research, and in particular photo-elicitation. The technique involves photos, videos and other forms of visual representation used in an interview, with informants asked to comment on the images. The aim is to promote more direct involvement of the informants in the research process and to encourage and stimulate the collection of quantitatively and qualitatively different information to that obtained in conventional interviews. The potential and limitations of this technique in the field are investigated, describing and discussing photo-elicitation data collection in the Maasai village of Mkuru in northern Tanzania to explore the use and preservation of natural resources. Results and methodological insights from the fieldwork are presented and discussed.

  9. Between participants, props and stage: Eliciting insights through interaction

    DEFF Research Database (Denmark)

    Cramer-Petersen, Claus Lundgaard; Marijnissen, Thomas

    2012-01-01

    How can we develop innovative concepts? The purpose of this paper is to investigate how generative prototype sessions can elicit so-called tacit and latent knowledge from participants through interaction and play. To illustrate this, a session from the design process will be described along with ...... an indiscernible blend of different types of knowledge, but that tacit and latent constitutes an important part.......How can we develop innovative concepts? The purpose of this paper is to investigate how generative prototype sessions can elicit so-called tacit and latent knowledge from participants through interaction and play. To illustrate this, a session from the design process will be described along with a...... brief take on current theories. It is discussed how practical tools and methods along with the dynamics occurring during such a session can translate actor knowledge to become useful throughout a the entire design process. The paper concludes that knowledge gained from generative prototype sessions is...

  10. An alternative approach for eliciting willingness-to-pay

    Directory of Open Access Journals (Sweden)

    Laura J. Damschroder

    2007-04-01

    Full Text Available Open-ended methods that elicit willingness-to-pay (WTP in terms of absolute dollars often result in high rates of questionable and highly skewed responses, insensitivity to changes in health state, and raise an ethical issue related to its association with personal income. We conducted a 2x2 randomized trial over the Internet to test 4 WTP formats: 1 WTP in dollars; 2 WTP as a percentage of financial resources; 3 WTP in terms of monthly payments; and 4 WTP as a single lump-sum amount. WTP as a percentage of financial resources generated fewer questionable values, had better distribution properties, greater sensitivity to severity of health states, and was not associated with income. WTP elicited on a monthly basis also showed promise.

  11. Arousal recognition system based on heartbeat dynamics during auditory elicitation.

    Science.gov (United States)

    Nardelli, Mimma; Valenza, Gaetano; Greco, Alberto; Lanata, Antonio; Scilingo, Enzo Pasquale

    2015-08-01

    This study reports on the recognition of different arousal levels, elicited by affective sounds, performed using estimates of autonomic nervous system dynamics. Specifically, as a part of the circumplex model of affect, arousal levels were recognized by properly combining information gathered from standard and nonlinear analysis of heartbeat dynamics, which was derived from the electrocardiogram (ECG). Affective sounds were gathered from the International Affective Digitized Sound System and grouped into four different levels of arousal. A group of 27 healthy volunteers underwent such elicitation while ECG signals were continuously recorded. Results showed that a quadratic discriminant classifier, as applied implementing a leave-one-subject-out procedure, achieved a recognition accuracy of 84.26%. Moreover, this study confirms the crucial role of heartbeat nonlinear dynamics for emotion recognition, hereby estimated through lagged Poincare plots. PMID:26737686

  12. Chitin elicitation of natural product production in marine bacteria

    DEFF Research Database (Denmark)

    Månsson, Maria; Wietz, Matthias; Larsen, Thomas Ostenfeld;

    glucose-based medium. The different phenotypic responses to a natural growth substrate may reflect different niche-adaptations or ecological functions of the compounds produced and it represents a fruitful approach for elicitation of natural product production in marine bacteria....... uncharacterized chemical potential of these organisms. As part of a new project on ecology-driven drug discovery at the Technical University of Denmark, we investigate the use of chitin to elicit or alter production of antibacterial compounds in marine bacteria. Within our large collection of Gram...... indicating that andrimid serves a function while growing on chitin-containing surfaces. In contrast, a Photobacterium halotolerans sustained production of all metabolites including the antibiotic holomycin. Furthermore, chitin stimulated the production of two potentially novel metabolites not observed on...

  13. Simplified Expert Elicitation Procedure for Risk Assessment of Operating Events

    Energy Technology Data Exchange (ETDEWEB)

    Ronald L. Boring; David Gertman; Jeffrey Joe; Julie Marble; William Galyean; Larry Blackwood; Harold Blackman

    2005-06-01

    This report describes a simplified, tractable, and usable procedure within the US Nuclear Regulator Commission (NRC) for seeking expert opinion and judgment. The NRC has increased efforts to document the reliability and risk of nuclear power plants (NPPs) through Probabilistic Risk Assessment (PRA) and Human Reliability Analysis (HRA) models. The Significance Determination Process (SDP) and Accident Sequence Precursor (ASP) programs at the NRC utilize expert judgment on the probability of failure, human error, and the operability of equipment in cases where otherwise insufficient operational data exist to make meaningful estimates. In the past, the SDP and ASP programs informally sought the opinion of experts inside and outside the NRC. This document represents a formal, documented procedure to take the place of informal expert elicitation. The procedures outlined in this report follow existing formal expert elicitation methodologies, but are streamlined as appropriate to the degree of accuracy required and the schedule for producing SDP and ASP analyses.

  14. Multiple Membrane Interactions and Versatile Vesicle Deformations Elicited by Melittin

    OpenAIRE

    Kingo Takiguchi; Michio Homma; Yasunori Yokoyama; Yohko Tanaka-Takiguchi; Tomoyoshi Takahashi; Fumimasa Nomura

    2013-01-01

    Melittin induces various reactions in membranes and has been widely studied as a model for membrane-interacting peptide; however, the mechanism whereby melittin elicits its effects remains unclear. Here, we observed melittin-induced changes in individual giant liposomes using direct real-time imaging by dark-field optical microscopy, and the mechanisms involved were correlated with results obtained using circular dichroism, cosedimentation, fluorescence quenching of tryptophan residues, and e...

  15. Affective monitoring: A generic mechanism for affect elicitation

    OpenAIRE

    Phaf, R. Hans; Rotteveel, Mark

    2012-01-01

    In this paper we sketch a new framework for affect elicitation, which is based on previous evolutionary and connectionist modeling and experimental work from our group. Affective monitoring is considered a local match–mismatch process within a module of the neural network. Negative affect is raised instantly by mismatches, incongruency, disfluency, novelty, incoherence, and dissonance, whereas positive affect follows from matches, congruency, fluency, familiarity, coherence, and resonance, at...

  16. UML for Early Requirements Elicitation: A Regulation based Approach

    OpenAIRE

    Regev, Gil; Wegmann, Alain

    2002-01-01

    Early requirements of information systems are often understood in terms of the elicitation of stakeholders' high-level goals to be supported by the system under discussion. Stakeholders' goals are considered as the ultimate explanation of requirements. It is assumed that the notion of a high-level goal is natural and that high-level goals need no explanation with regard to their origins. We believe that these assumptions result in the definition of inadequate goals. We propose an organization...

  17. Classical vs. crowdsourcing surveys for eliciting geographic relevance criteria

    OpenAIRE

    De Sabbata, Stefano; Alonso, Omar; Mizzaro, Stefano

    2012-01-01

    Geographic relevance aims to assess the relevance of physical entities (e.g., shops and museums) in geographic space for a mobile user in a given context, thereby shifting the focus from the digital world (the realm of classical information retrieval) to the physical world. We study the elicitation of geographic relevance criteria by means of both a classical survey and an Amazon Mechanical Turk (a crowdsourcing platform) survey. This allows us to obtain three results: first, we gather a set ...

  18. The Elicitation of Subjective Probabilities with Applications in Agricultural Economics

    OpenAIRE

    Patricia E. NORRIS; Randall A. Kramer

    1990-01-01

    Probability judgements are important components of decision making under uncertainty. In particular, economic decisions can be aided by assuring more accurate assessment of probabilities and more realistic modelling of economic problems through the inclusion of subjective probabilities. The purpose of this paper is to describe the techniques which can be used to elicit subjective probabilities and the ways in which these techniques can be incorporated into agricultural economics research. The...

  19. Gender difference in N170 elicited under oddball task

    OpenAIRE

    Choi, Damee; Egashira, Yuka; Takakura, Jun’ya; Motoi, Midori; Nishimura, Takayuki; Watanuki, Shigeki

    2015-01-01

    Background: Some studies have reported gender differences in N170, a face-selective event-related potential (ERP) component. This study investigated gender differences in N170 elicited under oddball paradigm in order to clarify the effect of task demand on gender differences in early facial processing. Findings: Twelve males and 10 females discriminated targets (emotional faces) from non-targets (emotionally neutral faces) under an oddball paradigm, pressing a button as quickly as possible in...

  20. Gender difference in N170 elicited under oddball task

    OpenAIRE

    Choi, Damee; Egashira, Yuka; Takakura, Jun’ya; Motoi, Midori; Nishimura, Takayuki; Watanuki, Shigeki

    2015-01-01

    Background Some studies have reported gender differences in N170, a face-selective event-related potential (ERP) component. This study investigated gender differences in N170 elicited under oddball paradigm in order to clarify the effect of task demand on gender differences in early facial processing. Findings Twelve males and 10 females discriminated targets (emotional faces) from non-targets (emotionally neutral faces) under an oddball paradigm, pressing a button as quickly as possible in r...

  1. [Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis].

    Science.gov (United States)

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-08-20

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients' quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work. PMID:27561803

  2. Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue

    International Nuclear Information System (INIS)

    Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy

  3. Eliciting Secondary Education Pupils’ Views on Euthanasia Through Argumentative Paragraphs

    Directory of Open Access Journals (Sweden)

    Melike OZER KESKIN

    2012-12-01

    Full Text Available This study aims to elicit secondary education pupils’ views on euthanasia based on a survey model and with a study group of 253 pupils in year 9 studying in the city of Ankara in the school year 2010-2011. The study makes use of a combination of qualitative and quantitative research techniques as well as a Questionnaire for Personal Particulars in order to clarify the pupils’ demographics in data collection, and scenarios based on ethical dilemmas about active and passive euthanasia in order to elicit their views on the issue.The pupils’ views were elicited through the argumentative paragraphs that they were asked to write on the situations given in the scenarios. Of the qualitative data analysis techniques, the content analysis method was selected for the analysis of the argumentative paragraphs on the scenarios. In light of the data yielded by the content analysis, the pupils’ basic ethical guidelines in their decision-making processes were studied taking into account such variables as gender, school type, and family’s income.

  4. T Cell Vaccination as an Immunotherapy for Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    JingwuZhang

    2004-01-01

    Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual's own T cellrepertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactionsof a variety of related surface molecules (1). It induces regulatory immune responses that closely resemble thein vivo situation where the immune system is challenged by clonal activation and expansion of given T cellpopulations in various autoimmune diseases. T cell vaccination provides a powerful means of eliciting naturalreactions of the immune system in response to clonal expansion of T cells, which can used as a therapeuticapproach to suppress or eliminate specific pathogenic autoreactive T cells in autoimmune conditions. Clinicaltrials using T cell vaccination to deplete autoreactive T cells in human autoimmune conditions have begun toreveal the pathologic relevance of various autoimmune T cell populations in the disease processes, providing aunique opportunity to test the autoimmune theories in a clinical setting. Cellular & Molecular Immunology.2004; 1(5):321-327.

  5. Oncolytic viruses as immunotherapy: progress and remaining challenges

    Directory of Open Access Journals (Sweden)

    Aurelian L

    2016-05-01

    Full Text Available Laure Aurelian Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA Abstract: Oncolytic viruses (OVs comprise an emerging cancer therapeutic modality whose activity involves both direct tumor cell lysis and the induction of immunogenic cell death (ICD. Cellular proteins released from the OV-lysed tumor cells, known as damage-associated molecular patterns and tumor-associated antigens, activate dendritic cells and elicit adaptive antitumor immunity. Interaction with the innate immune system and the development of long-lasting immune memory also contribute to OV-induced cell death. The degree to which the ICD component contributes to the clinical efficacy of OV therapy is still unclear. Modulation of a range of immune interactions may be beneficial or detrimental in nature and the interactions depend on the specific tumor, the site and extent of the disease, the immunosuppressive tumor microenvironment, the OV platform, the dose, time, and delivery conditions, as well as individual patient responses. To enhance the contribution of ICD, OVs have been engineered to express immunostimulatory genes and strategies have been developed to combine OV therapy with chemo- and immune-based therapeutic regimens. However, these approaches carry the risk that they may also be tolerogenic depending on their levels and the presence of other cytokines, their direct antiviral effects, and the timing and conditions of their expression. The contribution of autophagy to adaptive immunity, the ability of the OVs to kill cancer stem cells, and the patient’s baseline immune status are additional considerations. This review focuses on the complex and as yet poorly understood balancing act that dictates the outcome of OV therapy. We summarize current understanding of the OVs’ function in eliciting antitumor immunity and its relationship to therapeutic efficacy. Also discussed are the criteria involved in restraining antiviral

  6. The future costs of nuclear power using multiple expert elicitations: effects of RD&D and elicitation design

    Science.gov (United States)

    Díaz Anadón, Laura; Nemet, Gregory; Verdolini, Elena

    2013-09-01

    Characterization of the anticipated performance of energy technologies to inform policy decisions increasingly relies on expert elicitation. Knowledge about how elicitation design factors impact the probabilistic estimates emerging from these studies is, however, scarce. We focus on nuclear power, a large-scale low-carbon power option, for which future cost estimates are important for the design of energy policies and climate change mitigation efforts. We use data from three elicitations in the USA and in Europe and assess the role of government research, development, and demonstration (RD&D) investments on expected nuclear costs in 2030. We show that controlling for expert, technology, and design characteristics increases experts’ implied public RD&D elasticity of expected costs by 25%. Public sector and industry experts’ cost expectations are 14% and 32% higher, respectively than academics. US experts are more optimistic than their EU counterparts, with median expected costs 22% lower. On average, a doubling of public RD&D is expected to result in an 8% cost reduction, but the uncertainty is large. The difference between the 90th and 10th percentile estimates is on average 58% of the experts’ median estimates. Public RD&D investments do not affect uncertainty ranges, but US experts are less confident about costs than Europeans.

  7. The future costs of nuclear power using multiple expert elicitations: effects of RD and D and elicitation design

    International Nuclear Information System (INIS)

    Characterization of the anticipated performance of energy technologies to inform policy decisions increasingly relies on expert elicitation. Knowledge about how elicitation design factors impact the probabilistic estimates emerging from these studies is, however, scarce. We focus on nuclear power, a large-scale low-carbon power option, for which future cost estimates are important for the design of energy policies and climate change mitigation efforts. We use data from three elicitations in the USA and in Europe and assess the role of government research, development, and demonstration (RD and D) investments on expected nuclear costs in 2030. We show that controlling for expert, technology, and design characteristics increases experts’ implied public RD and D elasticity of expected costs by 25%. Public sector and industry experts’ cost expectations are 14% and 32% higher, respectively than academics. US experts are more optimistic than their EU counterparts, with median expected costs 22% lower. On average, a doubling of public RD and D is expected to result in an 8% cost reduction, but the uncertainty is large. The difference between the 90th and 10th percentile estimates is on average 58% of the experts’ median estimates. Public RD and D investments do not affect uncertainty ranges, but US experts are less confident about costs than Europeans. (letter)

  8. MRP3: a molecular target for human glioblastoma multiforme immunotherapy

    International Nuclear Information System (INIS)

    that the tumor-associated antigen MRP3 has potential use for prognosis and as a target for malignant glioma immunotherapy

  9. T-cell regulatory mechanisms in specific immunotherapy.

    Science.gov (United States)

    Jutel, Marek; Akdis, Cezmi A

    2008-01-01

    Allergen-specific immunotherapy (SIT) is the only treatment which leads to a lifelong tolerance against previously disease-causing allergens due to restoration of normal immunity against allergens. The description of T-regulatory (Treg) cells being involved in prevention of sensitization to allergens has led to great interest whether they represent a major target for allergen-SIT and whether it would be possible to manipulate Treg cells to increase its efficacy. Activationinduced cell death, anergy and/or immune response modulation by Treg cells are essential mechanisms of peripheral T-cell tolerance. There is growing evidence that anergy, tolerance and active suppression are not entirely distinct, but rather represent linked mechanisms possibly involving the same cells and multiple suppressor mechanisms. Skewing of allergen-specific effector T cells to Treg cells appears as a crucial event in the control of healthy immune response to allergens and successful allergen-SIT. The Treg cell response is characterized by abolished allergen- induced specific T-cell proliferation and suppressed Thelper (Th)1- and Th2-type cytokine secretion. In addition, mediators of allergic inflammation that trigger cAMP-associated G-protein-coupled receptors, such as histamine receptor-2, may contribute to peripheral tolerance mechanisms. The increased levels of interleukin-10 and transforming growth factor-Beta that are produced by Treg cells potently suppress IgE production, while simultaneously increasing production of non-inflammatory isotypes IgG4 and IgA, respectively. In addition, Treg cells directly or indirectly suppress effector cells of allergic inflammation such as mast cells, basophils and eosinophils. In conclusion, peripheral tolerance to allergens is controlled by multiple active suppression mechanisms. It is associated with regulation of antibody isotypes and effector cells to the direction of a healthy immune response. By the application of the recent knowledge in Treg

  10. The alpha immunotherapy - A successful solution in cancer treatment

    International Nuclear Information System (INIS)

    Full text: Radiation has been used in cancer therapy for many years. While, in the past the treatment involved mainly use of relatively low energy beta-emitters, more recently it was shown that isotopes emitting alpha particles have been more effective and selective against blood-borne cancers, widespread tumors and residual cells remaining after surgical intervention. This study shows that radioimmunotherapy (RIT) with α emitters may be therapeutically more effective than RIT with conventional β emitters. In the process of designing and developing the radioimmunotherapy procedures, the selection of the isotope is a major factor. This selection depends on a number of criteria and parameters, affecting usefulness and feasibility. Usefulness is directly related to the radiological performance of the ionising radiation in relation to tissue and its morphology, with a major distinction between the effects of alpha and beta-particles. Usefulness is also related to the pharmacodynamic performance of the isotope-carrier (e.g. antibody) complex, where the proper choice of isotope radiodecay half-life is essential. Feasibility depends on availability of the components in the isotope-ligand-carrier complex, and also on convenience and safety aspects in the preparation and the handling of the materials as well as in their application in patients. Alpha immunotherapy is based on emission of alpha particles by radionuclides. Due to its short physical t1/2, 213Bi appears to be especially suitable for use in conjunction with fast-clearing fragments; its 440-keV α emission also can be used for quantitation by external scintigraphy. Bismuth-213, a short-lived alpha particle emitting radionuclide, is generated from the decay of 225Ac, which has a half-life of 10 days. The development of a clinical 225Ac/213Bi generator and the preparation of a 213Bi radiolabeled antibody for radioimmunotherapy of leukemia is reported. Alpha emitting radionuclides are amongst the most promising

  11. Dynamic evaluation of the response to specific immunotherapy

    International Nuclear Information System (INIS)

    Full text: Objectives: Evaluate in vivo response to specific immunotherapy in maintenance status, with leukocytes labelled with 99mTc-HMPAO. Methods: The leukocytes were labelled with 99mTc-HMPAO using the standard technique. After resuspension the labelled white cells with cell-free plasma they were injected intravenously in a peripheral vein faraway from the place where the therapeutic allergen suspension was applied. The both two administration were made at the same time. Simultaneously with the two injections, a 90 min dynamic acquisition, at thorax level, 64x64 matrix, at two frame/minute in anterior view, was carried out through a gamma camera. Static images, 256x256, 5 minutes, at 2, 3, 4, 5, 6, 8 and 21 hours after injections, of thorax and pelvis in anterior view, were acquired. During the examination, the local erythema was monitored. Results: The results obtained show that 40 min after injection local inflammatory activity at the IT administration place, with a progressive increase of local activity. 60 minutes after injection, ascendant lymphatic drainage directed to the homolateral axillary region ant to the lymphoid tissue of the upper mediastinum and anterior region of the neck were visualized. The static images show a progressive improvement of the inflammatory area corresponding to the place where IT was applied, with individualization of focal supraclavicular areas, bilaterally. In the latter images, thoracic, mediastinal, bowel and upper cervical localizations, were observed. Discussion and conclusions: In the patients studied, the specific IT shows great efficiency linked with the tolerability to different allergens (provocation test) achieved and with a significant fall of the Prick reactivity. However, at the aqueous extract application place, the local erythema with papula is always less than 60 mm. In these patients, the inflammatory response was significantly bigger in depth, time dependent, even after complete disappearance of the erythema

  12. Structured Digital Storytelling for Eliciting Software Requirements in the ICT4D Domain

    OpenAIRE

    Sinnig, Daniel; Pitula, Kristina; Becker, Richard; Radhakrishnan, T.; Forbrig, Peter

    2010-01-01

    Due to the specific challenges that ICT4D projects present, conventional requirements elicitation techniques are often inapplicable or insufficient. We address this shortcoming by introducing structured digital storytelling (SDS) as an alternative elicitation technique especially suited for the ICD4D domain. SDS is supported by our mobile elicitation tool designed around the needs and capabilities of the targeted user population. We embed SDS in a requirements elicitation and specification pr...

  13. Developing Socio-Cultural Scaffolding Model to Elicit Learners's Speech Production

    Science.gov (United States)

    Englishtina, Inti

    2015-01-01

    This study is concerned with developing scaffolding model to elicit bilingual kindergarten children's English speech production. It is aimed at describing what the teachers need in eliciting their students' speech production; how a scaffolding model should be developed to elicit the children's speech production; and how effective is the…

  14. 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. PMID:27330810

  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. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    International Nuclear Information System (INIS)

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study

  17. BCG immunotherapy of bladder cancer: inhibition of tumor recurrence and associated immune responses.

    Science.gov (United States)

    Lamm, D L; Thor, D E; Winters, W D; Stogdill, V D; Radwin, H M

    1981-07-01

    Fifty-one patients with confirmed bladder cancer have enrolled in a prospective evaluation of BCG immunotherapy. Following resection of existing tumors, patients were stratified according to tumor grade and number of previous recurrences and randomly assigned to control or BCG treatment groups. Immunotherapy consisted of six weekly administrations of Pasteur strain BCG using 120 mg intravesically and 5 mg percutaneously. Immunotherapy side effects were minimal and no patient required postponement of BCG treatments. Eleven control (46%) compared with five (22%) BCG-treated patients had tumor recurrence (P = 0.078, chi 2). Prolongation of the disease-free interval with BCG treatment was significantly at the P = 0.016 level by Wilcoxon analysis. Four control and two BCG-treated patients had multiple recurrences. Comparing total episodes of recurrence, nineteen of 79 (24%) control and eight of 85 (7%) BCG group cystoscopic examinations revealed tumor (P = 0.006, chi 2). Immunologic correlates of response to immunotherapy were not statistically significant since only five BCG-treated patients had tumor recurrence. However, four of these five patients evidenced impaired LIF response to PPD at the time of tumor recurrence, and impairment of skin test reactivity and BCG humoral antibody response were more commonly seen in this subgroup of patients. PMID:7016300

  18. Antigen-specific immunotherapy in ovarian cancer and p53 as tumor antigen

    NARCIS (Netherlands)

    Vermeij, Renee; Leffers, Ninke; Melief, Cornelis J.; Daemen, Toos; Nijman, Hans W.

    2012-01-01

    This review discusses the results of different immunization strategies, identifies possible drawbacks in study design and provides potential solutions for augmentation of clinical efficacy. A potential target for cancer immunotherapy is p53, as approximately 50% of ovarian cancer cells carry p53 mut

  19. Clinical and laboratory 2-year outcome of oral immunotherapy in patients with cow's milk allergy.

    Science.gov (United States)

    Elizur, A; Appel, M Y; Goldberg, M R; Yichie, T; Levy, M B; Nachshon, L; Katz, Y

    2016-02-01

    Studies examining the long-term effect of oral immunotherapy in food-allergic patients are limited. We investigated cow's milk-allergic patients, >6 months after the completion of oral immunotherapy (n = 197). Questionnaires, skin prick tests, and basophil activation assays were performed. Of the 195 patients contacted, 180 (92.3%) were consuming milk protein regularly. Half experienced adverse reactions, mostly mild. Thirteen patients (6.7%) required injectable epinephrine. Higher reaction rate after immunotherapy was associated with more anaphylactic episodes before treatment and a lower starting dose (OR = 2.1, P = 0.035 and OR = 2.3, P = 0.035, respectively). Reaction rate in patients who were 6-15 months, 15-30 months, or >30 months post-treatment decreased from 0.28/month to 0.21/month to 0.15/month, respectively (P Milk-induced %CD63 and %CD203c expression was significantly lower in patients >24 months vs in patients <24 months post-treatment (P = 0.038 and P = 0.047, respectively). In conclusion, many patients experience mild adverse reactions after completing oral immunotherapy and some require injectable epinephrine. Progressive desensitization, both clinically and in basophil reactivity, occurs over time. PMID:26482941

  20. Advance of Cellular Immunotherapy in Clinical and Translational Medicine of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    YAN Fei; YU Shao-rong; FENG Ji-feng

    2016-01-01

    Lung cancer is one of the most common cancers and ranks the ifrst in the mortality worldwide. The core of immunotherapy, especially cellular immunotherapy, is to activate the T cell-mediated tumor-killing effect in patients with tumors, so as to increase their anti-tumor effect. Surgery and radio- and chemotherapy cannot radically eliminate cancerous cells, but immunotherapy is an important supplementary method in killing tumor stem cells and non-proliferating cells. Cellular immunotherapy contains dendritic cells (DC), cytokine-induced killer (CIK), DC-CIK, natural killer T cells (NKT) and γδ T cells, which provides new techniques for the comprehensive treatment of lung cancer. Using CIK combined with DC, radiochemotherapy, radiofrequency ablation and monomers of Chinese medicine to induce CIK cells that directionally migrate to cancerous nest can increase tumor-killing ability and immunoregulatory ability of CIK cells, reduce adverse and toxic reactions and increase patients’ quality of life, and NKT cell and γδ T cell therapies have also been gradually perfected and promoted in clinical translation. This study mainly introduced the clinical translation of DC vaccines, CIK cells and DC-CIK treatment for lung cancer, hoping to provide new pathways and reference for the clinical treatment of lung cancer.

  1. The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Mira A. Patel

    2014-09-01

    Full Text Available The current standard of care for glioblastoma (GBM is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ. As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.

  2. 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.

  3. The current role of sublingual immunotherapy in the treatment of allergic rhinitis in adults and children

    Directory of Open Access Journals (Sweden)

    Simonetta Masieri

    2011-02-01

    Full Text Available Cristoforo Incorvaia1, Simonetta Masieri2, Silvia Scurati3, Silvia Soffia3, Paola Puccinelli3, Franco Frati31Allergy/Pulmonary rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 2ENT Clinic, University La Sapienza, Rome, Italy; 3Medical and Scientific Department, Stallergenes, Milan, ItalyAbstract: Allergic rhinitis is a very common disease affecting about 20% of people. It may be treated by allergen avoidance when possible, by antiallergic drugs such as antihistamines and topical corticosteroids, and by allergen-specific immunotherapy. The latter is the only treatment able to act on the causes and not only on the symptoms of respiratory allergy and is able to maintain its efficacy even after stopping, provided an adequate duration of treatment of 3–5 years is ensured. Sublingual immunotherapy (SLIT was introduced in the 1990s as a possible solution to the problem of adverse systemic reactions to subcutaneous immunotherapy and has been demonstrated by more than 50 trials and globally evaluated thus far by five meta-analyses as an effective and safe treatment for allergic rhinitis. Life-threatening reactions are extremely rare. However, it is important to note that clinical efficacy occurs only if SLIT meets its needs, ie, sufficiently high doses are regularly administered for at least 3 consecutive years. This is often overlooked in the current practice and may prevent the same success reported by trials from being achieved.Keywords: allergic rhinitis, sublingual immunotherapy, efficacy, safety, compliance, meta-analysis 

  4. IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy

    Science.gov (United States)

    Helms, Mike W.; Prescher, Jennifer A.; Cao, Yu-An; Schaffert, Steven

    2016-01-01

    Cytokine-induced killer (CIK) cells are T cell derived ex vivo expanded cells with both NK and T cell properties. They exhibit potent anti-tumor efficacy against various malignancies in preclinical models and have proven safe and effective in clinical studies. We combined CIK cell adoptive immunotherapy with IL-12 cytokine immunotherapy in an immunocompetent preclinical breast cancer model. Combining CIK cells with IL-12 increased anti-tumor efficacy in vivo compared to either therapy alone. Combination led to full tumor remission and long-term protection in 75% of animals. IL-12 treatment sharply increased the anti-tumor efficacy of short-term cultured CIK cells that exhibited no therapeutic effect alone. Bioluminescence imaging based in vitro cytotoxicity and in vivo homing assays revealed that short-term cultured CIK cells exhibit full cytotoxicity in vitro, but display different tumor homing properties than fully expanded CIK cells in vivo. Our data suggest that short-term cultured CIK cells can be “educated” in vivo, producing fully expanded CIK cells upon IL-12 administration with anti-tumor efficacy in a mouse model. Our findings demonstrate the potential to improve current CIK cell-based immunotherapy by increasing efficacy and shortening ex vivo expansion time. This holds promise for a highly efficacious cancer therapy utilizing synergistic effects of cytokine and cellular immunotherapy. PMID:20532883

  5. Venom immunotherapy for preventing allergic reactions to insect stings : a systematic review and health economic analysis

    NARCIS (Netherlands)

    Boyle, R.; Elremeli, M.; Cherry, M.; Elberink, Oude J.; Bulsara, M.; Mahon, J.; Daniels, M.; Hockenhull, J.

    2012-01-01

    Background Venom immunotherapy (VIT) is commonly used for preventing further allergic reactions to insect stings in people who have had a sting reaction. The efficacy and safety of this treatment has not previously been assessed by a high-quality systematic review. Objectives To assess the effects o

  6. Measles, mumps and rubella vaccine as an intralesional immunotherapy in treatment of warts

    Directory of Open Access Journals (Sweden)

    Aarti N. Shah

    2016-02-01

    Conclusions: Intralesional immunotherapy with MMR vaccine was found to be a simple, effective, and safe treatment for warts. This study proved to be cost effective as patients can be treated with just 03 doses of MMR vaccine given at the interval of two weeks. [Int J Res Med Sci 2016; 4(2.000: 472-476

  7. Contribution of regulatory T cells to alleviation of experimental allergic asthma after specific immunotherapy

    NARCIS (Netherlands)

    Maazi, H.; Shirinbak, S.; Willart, M.; Hammad, H. M.; Cabanski, M.; Boon, L.; Ganesh, V.; Baru, A. M.; Hansen, G.; Lambrecht, B. N.; Sparwasser, T.; Nawijn, M. C.; van Oosterhout, A. J. M.

    2012-01-01

    Background Allergen-specific immunotherapy (SIT) has been used since 1911, yet its mechanism of action remains to be elucidated. There is evidence indicating that CD4+FOXP3+ regulatory T cells (Treg cells) are induced during SIT in allergic patients. However, the contribution of these cells to SIT h

  8. Oral immunotherapy for the treatment of peanut allergy: systematic review of six case series studies

    NARCIS (Netherlands)

    Sheikh, A.; Nurmatov, U.; Venderbosch, I.; Bischoff, E.W.

    2012-01-01

    BACKGROUND: Allergy to peanuts is associated with considerable morbidity and, in a minority of cases, mortality. Natural resolution to peanut allergy occurs in only a few cases, hence the need to find effective interventions. Peanut oral immunotherapy (OIT) is a potentially important new therapeutic

  9. Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Joris D. Veltman

    2010-01-01

    Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

  10. DNA methyltransferase inhibition increases efficacy of adoptive cellular immunotherapy of murine breast cancer.

    Science.gov (United States)

    Terracina, Krista P; Graham, Laura J; Payne, Kyle K; Manjili, Masoud H; Baek, Annabel; Damle, Sheela R; Bear, Harry D

    2016-09-01

    Adoptive T cell immunotherapy is a promising approach to cancer treatment that currently has limited clinical applications. DNA methyltransferase inhibitors (DNAMTi) have known potential to affect the immune system through multiple mechanisms that could enhance the cytotoxic T cell responses, including: upregulation of tumor antigen expression, increased MHC class I expression, and blunting of myeloid derived suppressor cells (MDSCs) expansion. In this study, we have investigated the effect of combining the DNAMTi, decitabine, with adoptive T cell immunotherapy in the murine 4T1 mammary carcinoma model. We found that expression of neu, MHC class I molecules, and several murine cancer testis antigens (CTA) was increased by decitabine treatment of 4T1 cells in vitro. Decitabine also increased expression of multiple CTA in two human breast cancer cell lines. Decitabine-treated 4T1 cells stimulated greater IFN-gamma release from tumor-sensitized lymphocytes, implying increased immunogenicity. Expansion of CD11b + Gr1 + MDSC in 4T1 tumor-bearing mice was significantly diminished by decitabine treatment. Decitabine treatment improved the efficacy of adoptive T cell immunotherapy in mice with established 4T1 tumors, with greater inhibition of tumor growth and an increased cure rate. Decitabine may have a role in combination with existing and emerging immunotherapies for breast cancer. PMID:27416831

  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. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis

    NARCIS (Netherlands)

    Dahl, Ronald; Kapp, Alexander; Colombo, Giselda; deMonchy, Jan G. R.; Rak, Sabina; Emminger, Waltraud; Rivas, Montserrat Fernandez; Ribel, Mette; Durham, Stephen R.

    2006-01-01

    Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. Obje

  13. The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Mira A.; Kim, Jennifer E.; Ruzevick, Jacob [Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Phipps Building Rm 123, Baltimore, MD 21287 (United States); Li, Gordon [Department of Neurosurgery, Stanford University Medical Center, 1201 Welch Rd., P309 MSLS, Stanford, CA 94305 (United States); Lim, Michael, E-mail: mlim3@jhmi.edu [Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Phipps Building Rm 123, Baltimore, MD 21287 (United States)

    2014-09-29

    The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.

  14. Specific immunotherapy can greatly reduce the need for systemic steroids in allergic rhinitis

    DEFF Research Database (Denmark)

    Aasbjerg, Kristian; Torp-Pedersen, C; Backer, V

    2012-01-01

    Worldwide, more than 400 million individuals have allergic rhinitis, which has a significant impact on the individual's general health. Most patients self-medicate with over-the-counter drugs, but severe cases need treatment with topical corticosteroids and/or immunotherapy (SCIT). Although the A...

  15. Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care

    NARCIS (Netherlands)

    Roder, Esther; Berger, Marjolein Y.; Hop, Wim C. J.; Bernsen, Roos M. D.; de Groot, Hans; van Wijk, Roy Gerth

    2007-01-01

    Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referra

  16. The number of FceRI receptors on basophils decreases during subcutaneous immunotherapy

    DEFF Research Database (Denmark)

    Schmid, J. M.; Dahl, R.; Hoffmann, H. J.

    2015-01-01

    Background: Allergen specific immunotherapy is the only disease modifying treatment of allergic diseases. It induces complex cellular and humoral changes leading to an inhibition of type-1 allergic reactions. Method: Twenty four young grass pollen allergic adults suffering from seasonal rhino-con...

  17. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Melanoma and Sarcoma Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

  18. Inmunoterapias para las adicciones a las drogas Immunotherapies for Drug Addictions

    Science.gov (United States)

    Montoya, Iván D.

    2008-01-01

    Immunotherapies in the form of vaccines (active immunization) or monoclonal antibodies (passive immunization) appear safe and a promising treatment approaches for some substance-related disorders. The mechanism of action of the antibody therapy is by preventing the rapid entry of drugs of abuse into the central nervous system. In theory, immunotherapies could have several clinical applications. Monoclonal antibodies may be useful to treat drug overdoses and prevent the neurotoxic effects of drugs by blocking the access of drugs to the brain. Vaccines may help to prevent the development of addiction, initiate drug abstinence in those already addicted to drugs, or prevent drug use relapse by reducing the pharmacological effects and rewarding properties of the drugs of abuse on the brain. Passive immunization with monoclonal antibodies has been investigated for cocaine, methamphetamine, nicotine, and phencyclidine (PCP). Active immunization with vaccines has been studied for cocaine, heroin, methamphetamine, and nicotine. These immunotherapies seem promising therapeutic tools and are at different stages in their development before they can be approved by regulatory agencies for the treatment of substance-related disorders. The purpose of this article is to review the current immunotherapy approaches with emphasis on the risks and benefits for the treatment of these disorders. PMID:18551223

  19. Local immunotherapy based on agonistic CD40 antibodies effectively inhibits experimental bladder cancer

    OpenAIRE

    Sandin, Linda C; Tötterman, Thomas H; Sara M. Mangsbo

    2014-01-01

    Local immunotherapy resurfaces in the field of cancer as a potential way to cure localized and metastatic disease with limited toxic effects. We have recently demonstrated that local administration of agonistic CD40 antibodies can cure localized as well as disseminated bladder neoplasms. This approach reduces the circulating concentrations of antibodies that would result from systemic delivery, hence resulting in limited toxicity.

  20. Immunoinformatics and modeling perspective of T cell epitope-based cancer immunotherapy: a holistic picture.

    Science.gov (United States)

    Mishra, Seema; Sinha, Subhata

    2009-12-01

    Cancer immunotherapy is fast gaining global attention with its unique position as a potential therapy showing promise in cancer prevention and cure. It utilizes the natural system of immunity as opposed to chemotherapy and radiotherapy that utilize chemical drugs and radiation, respectively. Cancer immunotherapy essentially involves treatment and/or prevention with vaccines in the form of peptide vaccines (T and B cell epitopes), DNA vaccines and vaccination using whole tumor cells, dendritic cells, viral vectors, antibodies and adoptive transfer of T cells to harness the body's own immune system towards the targeting of cancer cells for destruction. Given the time, cost and labor involved in the vaccine discovery and development, researchers have evinced interest in the novel field of immunoinformatics to cut down the escalation of these critical resources. Immunoinformatics is a relatively new buzzword in the scientific circuit that is showing its potential and delivering on its promise in expediting the development of effective cancer immunotherapeutic agents. This review attempts to present a holistic picture of our race against cancer and time using the science and technology of immunoinformatics and molecular modeling in T cell epitope-based cancer immunotherapy. It also attempts to showcase some problem areas as well as novel ones waiting to be explored where development of novel immunoinformatics tools and simulations in the context of cancer immunotherapy would be highly welcome. PMID:19795913

  1. Patient-recognition data-mining model for BCG-plus interferon immunotherapy bladder cancer treatment.

    Science.gov (United States)

    Shah, Shital C; Kusiak, Andrew; O'Donnell, Michael A

    2006-06-01

    Bladder cancer is the fifth most common malignant disease in the United States with an annual incidence of around 63,210 new cases and 13,180 deaths. The cost for providing care for patients with bladder cancer disease is high. Bladder cancer treatment options such as immunotherapy, chemotherapy, radiation therapy, transurethral resection, and cystectomy, are used with varying success rates. In this research, data from a nationwide bacillus Calmette-Gue rin (BCG) plus interferon-alpha (IFN-alpha) immunotherapy clinical trial was considered. Data mining algorithms were used to analyze the effectiveness of immunotherapy treatment and to understand the prominent parameters and their interactions. The extracted knowledge was used to build a patient recognition model for prediction of treatment outcomes. The data was analyzed to understand the impact of various parameters on the treatment outcome. A list of significant parameters such as cumulative tumor size, presence of residual disease, stages of prior bladder cancer, current state of bladder cancer, and the presence of current bladder cancer (T1) is provided. The decision-making approach outlined in the paper supplemented with additional knowledge bases will lead to a comprehensive analytical road map of the BCG/IFN-alpha immunotherapy treatment. It will provide individualized guidelines for each stage of the treatment as well as measure the success of the treatment. PMID:15978568

  2. Controlling T cell senescence in the tumor microenvironment for tumor immunotherapy

    OpenAIRE

    Ye, Jian; Peng, Guangyong

    2015-01-01

    Understanding molecular mechanisms involved in creating and sustaining the tumor suppressive microenvironment is critical for the development of novel antitumor therapeutic strategies. We have identified the induction of T cell senescence as a novel mechanism utilized by human tumor cells to induce immune suppression, and provided a new strategy using TLR8 ligands to reverse tumor immunosuppressive effects for tumor immunotherapy.

  3. The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy

    International Nuclear Information System (INIS)

    The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care

  4. 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.

  5. Effect of house dust mite immunotherapy on interleukin-10-secreting regulatory T cells in asthmatic children

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; XIANG Li; LIU Yong-ge; WANG Yong-hong; SHEN Kun-ling

    2010-01-01

    Background Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response.Interleukin-10 (IL-10) plays a crucial role in inducing allergen-specific tolerance.However the reports of the changes of IL-10 in house dust mite (HDM)-specific immunotherapy were varied.The aim of this study was to evaluate the function of IL-10-secreting regulatory T cells in asthma children successfully treated with HDM immunotherapy.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 27 patients following 1.5--2 years of HDM-specific immunotherapy (SIT, SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthmagroup).After 48 hours of in vitro stimulation with HDM extracts, IL-10-secreting regulatory T cells were measured by four colour flow cytometry.Sera were tested for allergen-specific IgG4 and IgE using the Immuno CAP 100 assay.Results PBMCs from children undergoing immunotherapy following HDM extracts stimuli produced significantly more IL-10 compared with the asthma group.The frequency of iTreg cells and aTreg cells increased in SIT group after HDM stimulation, while it was not affected in the asthma group.Among the iTreg cells and aTreg cells, the frequency of CD4+CD25-Foxp3-IL-10+ Treg cells increased the most which was 2 times higher than that in unstimulated cultures in SIT group.The levels of HDM-specific IgG4 of SIT group was significiently higher compared with asthma group, but there was no correlation of the levels of HDM-specific IgG4 and IL-10 secreting Treg cells.Conclusions HDM-specific immunotherapy can successfully upregulate the frequency of IL-10-secreting Treg cells.CD4+CD25-Foxp3-IL-10+ Treg cells may play a key role in inducing the immune tolerance in HDM-specific immunotherapy.

  6. Structured tradeoffs preference elicitation: Evaluating CRWMS design and operations

    International Nuclear Information System (INIS)

    Preliminary studies over the past few years have yielded multiple design and operations alternatives for the planned Civilian Radioactive Waste Management System (CRWMS). Waste isolation, pre-closure health and safety, and life cycle cost are among the many factors considered in developing these alternatives. The task of CRWMS designers is complicated by substantial heat and nuclear radiation energy output of the spent nuclear fuel and high level waste intended for disposal in an underground repository. Not only must the usual effectiveness, operability and cost objectives be balanced, but done so in the context of a constantly changing environment. Particular alternatives sometimes are favored by virtue of their outstanding performance relative to one of these factors. The Ultimate success of the potential repository, however, depends on reaching a defensible and traceable final decision through simultaneous and systematic weighing of all relevant factors. This paper documents the outcome of Structured Tradeoffs Preference (STP) elicitation as a method for the simultaneous and systematic weighing of factors relevant to repository thermal loading, waste package (WP) design, and emplacement mode decisions. The study provided a low-cost early indication of directions of further research on CRWMS design and operations likely to be most fruitful. The method of STP elicitation was utilized to avoid potential biases documented in other efforts which use only unstructured decision making, or open-quotes well-considered judgmentclose quotes. The STP elicitation procedure presented here complements the use of a parameter network-model pyramid suggested elsewhere in this proceedings to provide a framework for precisely articulating technical questions needing answers. It also forms an independent crosscheck of systems engineering study results and performance assessment modeling

  7. Integrating Effectiveness, Transparency and Fairness into a Value Elicitation Process

    International Nuclear Information System (INIS)

    As part of the evaluation of Canada's proposed nuclear fuel waste disposal concept, the Federal Environmental Assessment and Review Panel (FEARP) undertook an extensive, nation-wide public hearing process. The hearing process itself was contentious and has been criticized on numerous grounds. It is our contention that the fundamental weakness of the FEARP process was that it was designed as an information-based forum, as opposed to a value-based forum.' Our observations and analyses of these hearings indicate that the FEARP envisioned a different purpose and a different outcome of this process than the public in general. As a result, public acceptability for the Concept or even the assessment process itself was not garnered due to a failure in the process to identify, address and incorporate values. To address this, we proposed a seven-step value elicitation process specifically designed to assess public acceptability of the disposal concept. An unfortunate consequence of the flawed public consultation process employed by the FEARP is that it is unclear exactly what it is the public finds unacceptable. Both from discussions and observations, it is difficult to ascertain whether the unacceptability lies with the Concept itself and/or the process by which the Concept was to be assessed. As a result, there is uncertainty as to what questions should be asked and how should the 'unacceptability' be addressed. In other words, does Canada need a new concept? Does Canada need to develop a mechanism for assessing the public acceptability of the Concept? Or both? The inability of the current process to answer such fundamental questions demonstrates the importance of developing an effective public acceptability and consultation process. We submit that, to create an acceptable Public Participation mechanism, it is necessary to found the construction of such a mechanism on the principles of effectiveness, transparency and fairness. Moreover, we believe that the larger decision

  8. Expert Panel Elicitation of Seismicity Following Glaciation in Sweden

    International Nuclear Information System (INIS)

    The Swedish Radiation Protection Authority, the Swedish Nuclear Power Inspectorate and the Swedish Nuclear Fuel and Waste Management Company have jointly carried out a project on expert panel elicitation on the issue of glacial induced Swedish earthquakes. Following a broad nomination procedure, 5 experts were chosen by a selection committee of 4 professors within Earth sciences disciplines. The 5 experts presented judgments about the frequency of earthquakes greater the magnitude 6 within 10 km for two Swedish sites, Oskarshamn and Forsmark, in connection with a glaciation cycle. The experts' median value vas 0,1 earthquakes for one glaciation cycle

  9. Elicited Salience and Salience-Based Level-k

    OpenAIRE

    Wolff, Irenaeus

    2016-01-01

    A level-k model based on a specific salience-pattern is the only model in the literature that accounts for behaviour in hide-and-seek games. This paper presents nine different experiments designed to measure salience. The elicited salience patterns tend to be similar, but none of them is similar to the pattern needed to allow the level-k model explain the hide-and-seek data. When based on any of the empirical salience measures, the salience-based level-k model does not fit the data well. p...

  10. Expert Panel Elicitation of Seismicity Following Glaciation in Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Hora, Stephen; Jensen, Mikael (eds.)

    2005-12-15

    The Swedish Radiation Protection Authority, the Swedish Nuclear Power Inspectorate and the Swedish Nuclear Fuel and Waste Management Company have jointly carried out a project on expert panel elicitation on the issue of glacial induced Swedish earthquakes. Following a broad nomination procedure, 5 experts were chosen by a selection committee of 4 professors within Earth sciences disciplines. The 5 experts presented judgments about the frequency of earthquakes greater the magnitude 6 within 10 km for two Swedish sites, Oskarshamn and Forsmark, in connection with a glaciation cycle. The experts' median value vas 0,1 earthquakes for one glaciation cycle.

  11. 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.

  12. Microsatellite instability as a predictive factor for immunotherapy in malignant melanoma.

    Science.gov (United States)

    Kubecek, Ondrej; Trojanova, Petronela; Molnarova, Veronika; Kopecky, Jindrich

    2016-08-01

    Immunotherapy has attracted attention as a novel treatment modality for malignant melanoma. Although the use of immunotherapy in metastatic melanoma has shown promising results, there remains a lack of predictive biomarkers indicating treatment benefit from immunotherapy. There is growing evidence suggesting that microsatellite instability (MSI) as a product of DNA mismatch repair deficiency, may be one of possible predictive markers in malignant melanoma. It has been proposed that the immunogenicity of some tumors might be determined by mutational heterogeneity and could be the key to the success of immune therapies. This is also supported by the fact that tumors with the highest amount of somatic mutations, such as malignant melanoma have showed positive results with immune checkpoint inhibitors. There are promising data regarding the association between MSI status and immunogenicity from studies with colorectal cancer, where MSI is linked to improved prognosis compared to microsatellite stable cancers. MSI in colon cancer is linked to a significant increase of immunocompetent cells responsible for the antitumor activity - CD3(+), CD8(+), CD45RO(+), and T-bet(+) lymphocytes and decrease of inhibition factors such as Foxp3, IL-6, IL-17, and TGF-β. On the other hand, taking into account the progression-dependent accumulation of somatic mutations in MSI tumors and consequent high levels of neo-antigens, the possible drug resistance of MSI tumors to traditional treatment, and the presence of inhibition checkpoints within the MSI tumors, there is a solid rationale for the use of novel therapeutic strategies such as immunotherapy in MSI melanomas. We presume that the MSI phenotype in malignant melanoma might be helpful to identify patients, who would be more likely to profit from immunotherapy than from conventional therapy. PMID:27372860

  13. Medical-legal considerations in the practice of allergy: personal reflections on lessons learned from an immunotherapy fatality.

    Science.gov (United States)

    Hallett, Jeffrey S

    2004-01-01

    Fatalities after administration of specific allergen immunotherapy are rare occurrences in a general allergy practice, as is medical negligence litigation. The author has experienced both and now relates his personal reflections on the lessons that were learned from the experiences. The twelve lessons that are reviewed encompass observations that are relevant not only to immunotherapy litigation but also to any general medical negligence litigation that one might encounter. Three principles of practice that are specific for allergen immunotherapy administration and that were closely scrutinized during the litigation are also reviewed. PMID:15709451

  14. Present and future perspectives on immunotherapy for advanced renal cell carcinoma: Going to the core or beating around the bush?

    Directory of Open Access Journals (Sweden)

    Hidenori Kawashima

    2015-03-01

    Full Text Available Metastatic lesions of renal cell carcinoma (RCC occasionally regress spontaneously after surgical removal of the primary tumor. Although this is an exceptionally rare occurrence, RCC has thus been postulated to be immunogenic. Immunotherapies, including cytokine therapy, peptide-based vaccines, and immune checkpoint inhibitors have therefore been used to treat patients with advanced, metastatic RCC. We review the history, trends, and recent progress in immunotherapy for advanced RCC and discuss future perspectives, with consideration of our experimental work on galectin 9 and PINCH as promising specific immunotherapy targets. 

  15. Eliciting and communicating expert judgments: Methodology and application to nuclear safety

    International Nuclear Information System (INIS)

    The most ambitious and certainly the most extensive formal expert judgment process was the elicitation of numerous events and uncertain quantities for safety issues in five nuclear power plants in the U.S. The general methodology for formal expert elicitations are described. An overview of the expert elicitation process of NUREG 1150 is provided and the elicitation of probabilities for the interfacing systems loss of coolant accident LOCA (ISL) in PWRs is given as an example of this elicitation process. Some lessons learned from this study are presented. (DG)

  16. T Cell Vaccination as an Immunotherapy for Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    Jingwu Zhang

    2004-01-01

    Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual's own T cell repertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactions of a variety of related surface molecules (1). It induces regulatory immune responses that closely resemble the in vivo situation where the immune system is challenged by clonal activation and expansion of given T cell populations in various autoimmune diseases. T cell vaccination provides a powerful means of eliciting natural reactions of the immune system in response to clonal expansion of T cells, which can used as a therapeutic approach to suppress or eliminate specific pathogenic autoreactive T cells in autoimmune conditions. Clinical trials using T cell vaccination to deplete autoreactive T cells in human autoimmune conditions have begun to reveal the pathologic relevance of various autoimmune T cell populations in the disease processes, providing a unique opportunity to test the autoimmune theories in a clinical setting. Cellular & Molecular Immunology.2004;1(5):321-327.

  17. An expert elicitation of climate, energy and economic uncertainties

    International Nuclear Information System (INIS)

    Critical energy policy decisions rely on expert assessments of key future uncertainties. But existing modelling techniques that help form these expert assessments often ignore the existence of uncertainty. Consequently, techniques to measure these uncertainties are of increasing importance. We use one technique, expert elicitation, to assess six key uncertain parameters with 25 UK energy experts across academia, government and industry. We obtain qualitative descriptions of the uncertain parameters and a novel data set of probability distributions describing individual expert beliefs. We conduct a sensitivity analysis on weights for a linear opinion pool and show that aggregated median beliefs in 2030 are: for oil price $120/barrel (90% CI: 51, 272); for greenhouse gas price $34/tCO2e (90% CI: 5, 256) and for levelised cost of low-carbon electricity 17.1 US cents/kWh (90% CI: 8.3, 31.0). The quantitative results could inform model validation, help benchmark policy makers’ beliefs or provide probabilistic inputs to models. - Highlights: • We conduct an expert elicitation of 25 UK energy experts from academia, industry and government. • We obtained expert beliefs for six national and international drivers of energy demand. • A linear pool of expert beliefs on oil price in 2030 is insensitive to correlation between the experts. • Experts agree on dependence structure of energy uncertainties, but individual assessments of future values exhibit variation

  18. Emotion elicitation: A comparison of pictures and films

    Directory of Open Access Journals (Sweden)

    Meike Katrin Uhrig

    2016-02-01

    Full Text Available AbstractPictures and film clips are widely used and accepted stimuli to elicit emotions. Based on theoretical arguments it is often assumed that the emotional effects of films exceed those of pictures, but to date this assumption has not been investigated directly. The aim of the present study was to compare pictures and films in terms of their capacity to induce emotions verified by means of explicit measures. Stimuli were (a single pictures presented for 6 s, (b a set of three consecutive pictures with emotionally congruent contents presented for 2 s each, (c short film clips with a duration of 6 s. A total of 144 participants rated their emotion and arousal states following stimulus presentation. Repeated-measures ANOVAs revealed that the film clips and 3-picture version were as effective as the classical 1-picture method to elicit positive emotions, however, modulation towards positive valence was little. Modulation toward negative valence was more effective in general. Film clips were less effective than pictorial stimuli in producing the corresponding emotion states (all p < .001 and were less arousing (all p ≤ .02. Possible reasons for these unexpected results are discussed.

  19. Emotion Elicitation: A Comparison of Pictures and Films.

    Science.gov (United States)

    Uhrig, Meike K; Trautmann, Nadine; Baumgärtner, Ulf; Treede, Rolf-Detlef; Henrich, Florian; Hiller, Wolfgang; Marschall, Susanne

    2016-01-01

    Pictures and film clips are widely used and accepted stimuli to elicit emotions. Based on theoretical arguments it is often assumed that the emotional effects of films exceed those of pictures, but to date this assumption has not been investigated directly. The aim of the present study was to compare pictures and films in terms of their capacity to induce emotions verified by means of explicit measures. Stimuli were (a) single pictures presented for 6 s, (b) a set of three consecutive pictures with emotionally congruent contents presented for 2 s each, (c) short film clips with a duration of 6 s. A total of 144 participants rated their emotion and arousal states following stimulus presentation. Repeated-measures ANOVAs revealed that the film clips and 3-picture version were as effective as the classical 1-picture method to elicit positive emotions, however, modulation toward positive valence was little. Modulation toward negative valence was more effective in general. Film clips were less effective than pictorial stimuli in producing the corresponding emotion states (all p < 0.001) and were less arousing (all p ≤ 0.02). Possible reasons for these unexpected results are discussed. PMID:26925007

  20. Vibrio elicits targeted transcriptional responses from copepod hosts.

    Science.gov (United States)

    Almada, Amalia A; Tarrant, Ann M

    2016-06-01

    Copepods are abundant crustaceans that harbor diverse bacterial communities, yet the nature of their interactions with microbiota are poorly understood. Here, we report that Vibrio elicits targeted transcriptional responses in the estuarine copepod Eurytemora affinis We pre-treated E. affinis with an antibiotic cocktail and exposed them to either a zooplankton specialist (Vibrio sp. F10 9ZB36) or a free-living species (Vibrio ordalii 12B09) for 24 h. We then identified via RNA-Seq a total of 78 genes that were differentially expressed following Vibrio exposure, including homologs of C-type lectins, chitin-binding proteins and saposins. The response differed between the two Vibrio treatments, with the greatest changes elicited upon inoculation with V. sp. F10 We suggest that these differentially regulated genes play important roles in cuticle integrity, the innate immune response, and general stress response, and that their expression may enable E. affinis to recognize and regulate symbiotic vibrios. We further report that V. sp. F10 culturability is specifically altered upon colonization of E. affinis These findings suggest that rather than acting as passive environmental vectors, copepods discriminately interact with vibrios, which may ultimately impact the abundance and activity of copepod-associated bacteria. PMID:27056917

  1. Changes in gene expression induced by Micro-Immunotherapy

    Directory of Open Access Journals (Sweden)

    Maurice Jeaner

    2012-09-01

    Full Text Available Background: Metabolic syndrome (MS is a metabolic disorder associated with obesity, type-II diabetes, and “low grade inflammation”, with the concomitant increased risk of cardiovascular events. As a chronic inflammatory process, MS results in a dysregulation of the cytokine profile. 2L®INFLAM, a Micro-immunotherapy (MI medication formulated with highly diluted cytokines, is currently prescribed in Belgium for inflammatory diseases and potentially may be helpful for MS patients. Aims: To investigate the impact of 2L®INFLAM on selected gene expression markers (mRNA in patients suffering from MS, in addition to biological and clinical parameters. Methodology: Four well characterized MS adult patients with stabilized body-weight were advised to take one capsule of 2L®INFLAM per day (by sublingual-oral route for 6 months (composition in table 1. Concomitantly to biological and clinical examination, genes expression status was assessed by a DNA microarray technology (Oxygen™ comprising 200 genes involved mainly in oxidative stress and inflammation. Whole blood collection was performed before and after treatment (3-6 months and mRNA levels measured. Gene expression was classified in 3 series (normally expressed, up or down-regulated and genes related to diabetes predisposition were scored by using a proprietary Diascore (Probiox. Results: Before MI medication, a significant percentage of dysregulated genes (median: 16.3% as well as a positive Diascore (median: 1.6 were noticed. Impressive correction of dysregulated genes (reaching 90% for one patient was observed after 3 months of treatment (median: 2.3% in addition to an improvement of Diascore in 3 MS patients out of 4 (median: 0.5. During the same period, both clinical and biological parameters remained unchanged. Conclusions: MS patients showing a high level of gene dysregulation efficiently normalized after 3 months of 2L

  2. Specific immunotherapy (SIT in the treatment of allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Gorenoi, Vitali

    2010-03-01

    Full Text Available Scientific background: Allergic rhinitis (AR exhibits a prevalence of approx. 20% in Germany and causes enormous costs in the health care system. Specific immunotherapy (SIT is considered to be the only potentially causal therapy for AR and mainly administered by two routes, subcutaneous (SCIT and sublinguale (SLIT. SIT promises a reduction of symptoms and the need for medication in patients with AR. Research questions: The question arises, to what extent is SIT effective and cost effective in the treatment of AR and which ethical-social and legal aspects have to be considered regarding its application. Methods: The literature search was accomplished in the electronic data bases MEDLINE, EMBASE etc. in February 2008. The medical evaluation was based on systematic reviews of blinded, randomised controlled studies (RCT. The economic evaluation included health-economic studies on the basis of RCT. Additionally, it was also searched for publications explicitly addressing ethical-social and legal aspects of the use of SIT. Results: Medical evaluationTwo reviews on SCIT and three on SLIT were included in the medical evaluation. For the evaluation of SIT with grass pollen results for short and medium-term effects are considered from several studies, for SIT with other seasonal allergens (e. g. tree pollen and with house dust mite allergens from clearly fewer studies and for SIT with other perennial allergens only from a few. The reviews report a significant reduction of the symptom and medication score in favour of SCIT with seasonal allergens and recognise the effectiveness at least for grass pollen allergens. Also for other seasonal allergens SCIT is appraised as effective. The reviews about SLIT determine a significant reduction of the symptom and the medication score in favour of SLIT vs. placebo in short and medium term follow-up in evaluations across all allergens. The subgroup analyses show a significant reduction of the symptom and medication

  3. Dendritic cells and cytokines as adjuvants for immunotherapy of tumours associated with human papilloma virus type 16

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan; Vonka, V.; Šímová, Jana; Šmahel, M.; Indrová, Marie; Mikyšková, Romana

    Amsterdam, 2002. s. -. [Immunopotentiators in modern vaccines .. 14.05.2002-16.05.2002, Praha] Institutional research plan: CEZ:AV0Z5052915 Keywords : dendritic cells * interleukins * immunotherapy Subject RIV: EB - Genetics ; Molecular Biology

  4. Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances

    Directory of Open Access Journals (Sweden)

    Simpson GR

    2016-01-01

    Full Text Available Guy R Simpson,1 Kate Relph,1 Kevin Harrington,2 Alan Melcher,3 Hardev Pandha1 1Department of Clinical and Experimental Medicine, Targeted Cancer Therapy, Faculty of Health and Medical Sciences, University of Surrey, Guildford, 2Targeted Therapy, The Institute of Cancer Research/The Royal Marsden NIHR Biomedical Research Centre, London, 3Targeted and Biological Therapies,Oncology and Clinical Research, Leeds Institute of Cancer and Pathology, Faculty of Medicine and Health, University of Leeds, Leeds, UK Abstract: Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors. Similarly to oncolytic viruses, the benefits of chemotherapeutic agents may be that they induce systemic antitumor immunity through the induction of immunogenic cell death of cancer cells. Combining these two treatment modalities has to date resulted in significant potential in vitro and in vivo synergies through various mechanisms without any apparent additional toxicities. Chemotherapy has been and will continue to be integral to the management of advanced cancers. This review therefore focuses on the potential for a number of common cytotoxic agents to be combined with clinically relevant oncolytic viruses. In many cases, this combined approach has already advanced to the clinical trial arena. Keywords: oncolytic virotherapy, chemotherapy, immunogenic cell death

  5. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    Directory of Open Access Journals (Sweden)

    Moral A

    2016-06-01

    Full Text Available Angel Moral,1 Victoria Moreno,2 Francisco Girón,3 David El-Qutob,4 José D Moure,5 Manuel Alcántara,6 Antonia Padial,7 Alberto G Oehling,8 Carmen Millán,9 Fernando de la Torre10 1Allergy Service, Hospital Virgen del Valle, Toledo, 2Allergy Service, Hospital Blanca Paloma, Huelva, 3Consulta Privada, Granada, 4Allergy Service, Clínica Atenea, Castellón, 5Pediatric Department, Complejo Hospitalario Universitario de Santiago, A Coruña, 6Allergy Service, Complejo Hospitalario de Jaén, Jaén, 7Allergy Service, Hospital Infanta Sofía, Madrid, 8Centro de Alergia y Asma Balear, Mallorca, 9Consulta Privada, Cádiz, 10ALK-Abelló, SA, Madrid, Spain Background: Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy.Patients and methods: A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months.Results: The most frequent adverse reaction was oral pruritus (13.7% of the patients. Most of the reactions were local (84.7% and immediate (93.5% and occurred during the initiation phase (60.6%. All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417, age (P=0.1801, years since the disease was first

  6. Myeloma cell line–derived, pooled heat shock proteins as a universal vaccine for immunotherapy of multiple myeloma

    OpenAIRE

    Qian, Jianfei; Hong, Sungyoul; Wang, Siqing; Zhang, Liang; Sun, Luhong; Wang, Michael; Yang, Jing; Kwak, Larry W.; Hou, Jian; Yi, Qing

    2009-01-01

    Tumor cell–derived heat shock proteins are used as vaccines for immunotherapy of cancer patients. However, current approaches require the generation of custom-made products and are clinically ineffective. To improve the applicability of heat shock protein–based immunotherapy in cancers and to enhance clinical efficacy, we explored combinational treatments in a myeloma setting using pooled heterogeneous or allogeneic myeloma cell line–derived glycoprotein 96 (gp96) as universal vaccines, and c...

  7. 205 Allergy Training and Immunotherapy in Latin America: How Survey-Results Lead to a Regional Overview

    OpenAIRE

    Gomez, R. Maximiliano; Linnemann, Désirée Larenas; Passalacqua, Giovanni; González-Díaz, Sandra; Coce, Victor H.; Canonica, Giorgio Walter; Baena-Cagnani, Carlos E

    2012-01-01

    Background In April 2011 a group of Latin American (LA) allergy experts, leaders in their countries in the area of immunotherapy, met in Cordoba, Argentina, to discuss how allergy and allergen-specific immunotherapy (ASIT) can be improved in the region. The need for a situational sketch was expressed. Methods A questionnaire on allergy training (AT), ASIT, extracts and legislation was sent out to 22 leaders in the field of nine LA countries to obtain an overview of the LA situation. Results R...

  8. Elicitation: A Tool for Enriching the Bioactive Composition of Foods

    Directory of Open Access Journals (Sweden)

    Nieves Baenas

    2014-09-01

    Full Text Available Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant cell adaptation to the environment, specific organoleptic properties of foods, and protective effects in human cells against oxidative processes in the development of neurodegenerative and cardiovascular diseases and certain types of cancer. Biotic (biological origin, abiotic (chemical or physical origin elicitors and phytohormones have been applied alone or in combinations, in hydroponic solutions or sprays, and in different selected time points of the plant growth or during post-harvest. Understanding how plant tissues and their specific secondary metabolic pathways respond to specific treatments with elicitors would be the basis for designing protocols to enhance the production of secondary metabolites, in order to produce quality and healthy fresh foods.

  9. Eliciting design patterns for e-learning systems

    Science.gov (United States)

    Retalis, Symeon; Georgiakakis, Petros; Dimitriadis, Yannis

    2006-06-01

    Design pattern creation, especially in the e-learning domain, is a highly complex process that has not been sufficiently studied and formalized. In this paper, we propose a systematic pattern development cycle, whose most important aspects focus on reverse engineering of existing systems in order to elicit features that are cross-validated through the use of appropriate, authentic scenarios. However, an iterative pattern process is proposed that takes advantage of multiple data sources, thus emphasizing a holistic view of the teaching learning processes. The proposed schema of pattern mining has been extensively validated for Asynchronous Network Supported Collaborative Learning (ANSCL) systems, as well as for other types of tools in a variety of scenarios, with promising results.

  10. Safety and Efficacy of Nucleic Acid Polymers in Monotherapy and Combined with Immunotherapy in Treatment-Naive Bangladeshi Patients with HBeAg+ Chronic Hepatitis B Infection

    Science.gov (United States)

    Al-Mahtab, Mamun; Bazinet, Michel; Vaillant, Andrew

    2016-01-01

    Previous in vivo studies have suggested that nucleic acid polymers (NAPs) may reduce circulating levels of HBsAg in the blood by blocking its release from infected hepatocytes and that this effect may have clinical benefit. NAP treatment, was evaluated in two clinical studies in patients with HBeAg positive chronic HBV infection. The REP 101 study examined REP 2055 monotherapy in 8 patients and the REP 102 study examined REP 2139-Ca, in monotherapy in 12 patients, 9 of which transitioned to short term combined treatment with pegylated interferon alpha 2a or thymosin alpha 1. In both studies NAP monotherapy was accompanied by 2–7 log reductions of serum HBsAg, 3–9 log reductions in serum HBV DNA and the appearance of serum anti-HBsAg antibodies (10–1712 mIU / ml). Eight of the 9 patients transitioning to combined treatment with immunotherapy (pegylated interferon or thymosin alpha 1) in the REP 102 study experienced HBsAg loss and all 9 patients experienced substantial increases in serum anti-HBsAg antibody titers before withdrawal of therapy. For 52 weeks after removal of REP 2055 therapy, rebound of serum viremia (HBV DNA > 1000 copies / ml, HBsAg > 1IU / ml) was not observed in 3 / 8 patients. Suppression of serum virema was further maintained for 290 and 231 weeks in 2 of these patients. After withdrawal of all therapy in the 9 patients that transitioned to combination therapy in the REP 102 study, 8 patients achieved HBV DNA Viral rebound occurred over a period of 12 to 123 weeks in 7 patients but was still absent in two patients at 135 and 137 weeks of follow-up. Administration tolerability issues observed with REP 2055 were rare with REP 2139-Ca but REP 2139-Ca therapy was accompanied by hair loss, dysphagia and dysgeusia which were considered related to heavy metal exposure endemic at the trial site. These preliminary studies suggest that NAP can elicit important antiviral responses during treatment which may improve the effect of immunotherapy. NAPs

  11. Knowledge elicitation techniques and application to nuclear plant maintenance

    Science.gov (United States)

    Doyle, E. Kevin

    The new millennium has brought with it the opportunity of global trade which in turn requires the utmost in efficiency from each individual industry. This includes the nuclear power industry, a point which was emphasized when the electrical generation industry began to be de regulated across North America the late 1990s and re-emphasized when the northeast power grid of North America collapsed in the summer of 2003. This dissertation deals with reducing the cost of the maintenance function of Candu nuclear power plants and initiating a strong link between universities and the Canadian nuclear industry. Various forms of RCM (reliability-centred maintenance) have been the tools of choice in industry for improving the maintenance function during the last 20 years. In this project, pilot studies, conducted at Bruce Power between 1999 and 2005, and reported on in this dissertation, lay out a path to implement statistical improvements as the next step after RCM in reducing the cost of the maintenance. Elicitation protocols, designed for the age group being elicited, address the much-documented issue of a lack of data. Clear, graphical, inferential statistical interfaces are accentuated and developed to aid in building the teams required to implement the various methodologies and to help in achieving funding targets. Graphical analysis and Crow/AMSAA (army materials systems analysis activity) plots are developed and demonstrated from the point of view of justifying the expenditures of cost reduction efforts. This dissertation ultimately speaks to the great opportunity being presented by this approach at this time: of capturing the baby-boom generation's huge pool of knowledge before those people retire. It is expected that the protocols and procedures referenced here will have applicability across the many disciplines where collecting expert information from a similar age group is required.

  12. Promoting environmental sustainability via an expert elicitation process

    International Nuclear Information System (INIS)

    Environmental sustainability (ES) planning was applied to the 981-mile, commercially navigable Ohio River. Navigation improvement needs were identified within the broad study along with actions to restore aquatic and riparian ecological resources to a higher state of sustainability. The actions were identified via an Expert Elicitation Process (EEP) involving aquatic and riparian/terrestrial experts knowledgeable of Ohio River resources. The received information was synthesized into goals for the selected resources (Valued Ecosystem Components - or VECs), actions or measures to attain the goals, and monitoring to evaluate conditions. Finally, 26 types of ES actions were identified and classified into three ES alternatives. These alternatives were then evaluated relative to key decision criteria, and such evaluations, based on pertinent decision criteria, were also conducted for four navigation improvement alternatives. Finally, the best combination of ES and navigation alternatives was identified. The key lessons derived from this use of EEP were that: (1) EEP can support the preliminary identification of ES measures; however, more detailed study of specific designs and cost evaluations will be necessary; (2) the method promotes collaboration between key scientists and policymakers from governmental agencies and private sectors, and such collaboration will ultimately provide the foundation for implementation of sustainability actions; and (3) an effective EEP does not occur by accident, it requires careful planning, implementation, and documentation. - Research Highlights: → Use of an Expert Elicitation Process (EEP) is demonstrated in this study. → EEP was used to identify Environmental Sustainability (ES) needs for the Ohio River. → EEP helped develop consensus among resource experts on ES needs. → EEP promotes collaboration to identify and contribute to common resource goals. → EEP may be used in assessing cumulative effects and formulating restoration

  13. Chimeric antigen receptor engineering: a right step in the evolution of adoptive cellular immunotherapy.

    Science.gov (United States)

    Figueroa, Jose A; Reidy, Adair; Mirandola, Leonardo; Trotter, Kayley; Suvorava, Natallia; Figueroa, Alejandro; Konala, Venu; Aulakh, Amardeep; Littlefield, Lauren; Grizzi, Fabio; Rahman, Rakhshanda Layeequr; Jenkins, Marjorie R; Musgrove, Breeanna; Radhi, Saba; D'Cunha, Nicholas; D'Cunha, Luke N; Hermonat, Paul L; Cobos, Everardo; Chiriva-Internati, Maurizio

    2015-03-01

    Cancer immunotherapy comprises different therapeutic strategies that exploit the use of distinct components of the immune system, with the common goal of specifically targeting and eradicating neoplastic cells. These varied approaches include the use of specific monoclonal antibodies, checkpoint inhibitors, cytokines, therapeutic cancer vaccines and cellular anticancer strategies such as activated dendritic cell (DC) vaccines, tumor-infiltrating lymphocytes (TILs) and, more recently, genetically engineered T cells. Each one of these approaches has demonstrated promise, but their generalized success has been hindered by the paucity of specific tumor targets resulting in suboptimal tumor responses and unpredictable toxicities. This review will concentrate on recent advances on the use of engineered T cells for adoptive cellular immunotherapy (ACI) in cancer. PMID:25901860

  14. Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy

    DEFF Research Database (Denmark)

    Zuidmeer-Jongejan, Laurian; Huber, Hans; Swoboda, Ines;

    2015-01-01

    BACKGROUND: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. OBJECTIVES: Preclinical characterization and good manufacturing practice (GMP) production...... chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural...... and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product. RESULTS: Purified mCyp c 1 behaves as...

  15. Optimizing complement-activating antibody-based cancer immunotherapy: a feasible strategy?

    Directory of Open Access Journals (Sweden)

    Maio Michele

    2004-06-01

    Full Text Available Abstract Passive immunotherapy with monoclonal antibodies (mAb targeted to specific tumor-associated antigens is amongst the most rapidly expanding approaches to biological therapy of cancer. However, until now a limited number of therapeutic mAb has demonstrated clinical efficacy in selected neoplasia. Results emerging from basic research point to a deeper characterization of specific biological features of neoplastic cells as crucial to optimize the clinical potential of therapeutic mAb, and to identify cancer patients who represent the best candidates to antibody-based immunotherapy. Focus on the tissue distribution and on the functional role of membrane complement-regulatory proteins such as Protectin (CD59, which under physiologic conditions protects tissues from Complement (C-damage, might help to optimize the efficacy of immunotherapeutic strategies based on C-activating mAb.

  16. Pancreatitis Secondary to Anti-Programmed Death Receptor 1 Immunotherapy Diagnosed by FDG PET/CT.

    Science.gov (United States)

    Alabed, Yazan Z; Aghayev, Ayaz; Sakellis, Christopher; Van den Abbeele, Annick D

    2015-11-01

    A 57-year-old man with metastatic melanoma developed colitis secondary to ipilimumab, a known immune-related adverse event (irAE). The patient then received pembrolizumab immunotherapy, an anti-programmed-death-receptor-1 (PD-1) antibody. Restaging FDG PET/CT study following 3 cycles of therapy demonstrated diffuse increased FDG uptake throughout the body of the pancreas associated with fat stranding in the peripancreatic region, suggestive of pembrolizumab-induced pancreatitis. Although the patient was clinically asymptomatic, diagnosis was biochemically confirmed with elevated amylase and lipase levels. In the era of immunotherapy, it will be critical to recognize irAEs early to allow prompt initiation of appropriate therapy and reduce the risk of long-term sequelae. PMID:26284765

  17. 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.

  18. BCG vaccine for immunotherapy in warts: is it really safe in a tuberculosis endemic area?

    Science.gov (United States)

    Daulatabad, Deepashree; Pandhi, Deepika; Singal, Archana

    2016-05-01

    Management of recurrent and or recalcitrant warts can be a therapeutic challenge and in such cases invoking body's own immunity may help to overcome the present episode and also prevent recurrences. Bacilli Calmette Geurin (BCG) immunotherapy has long been considered to be an effective and safe modality in such cases. We present a series of seven cases treated with BCG immunotherapy wherein a single dose of BCG caused regression of wart in 85.7% patients and complete resolution was evident in 28.6% patients. However, the development of adverse effects precluded any further dosages in four of seven (57.1%) patients. This raises serious concern on the safety of this therapeutic modality, especially in a population endemic to tuberculosis. PMID:26809285

  19. An update on antibody-based immunotherapies for Clostridium difficile infection

    Science.gov (United States)

    Hussack, Greg; Tanha, Jamshid

    2016-01-01

    Clostridium difficile continues to be one of the most prevalent hospital-acquired bacterial infections in the developed world, despite the recent introduction of a novel and effective antibiotic agent (fidaxomicin). Alternative approaches under investigation to combat the anaerobic Gram-positive bacteria include fecal transplantation therapy, vaccines, and antibody-based immunotherapies. In this review, we catalog the recent advances in antibody-based approaches under development and in the clinic for the treatment of C. difficile infection. By and large, inhibitory antibodies that recognize the primary C. difficile virulence factors, toxin A and toxin B, are the most popular passive immunotherapies under investigation. We provide a detailed summary of the toxin epitopes recognized by various antitoxin antibodies and discuss general trends on toxin inhibition efficacy. In addition, antibodies to other C. difficile targets, such as surface-layer proteins, binary toxin, motility factors, and adherence and colonization factors, are introduced in this review. PMID:27536153

  20. Regulatory T cell effects in antitumor laser immunotherapy: a mathematical model and analysis

    Science.gov (United States)

    Dawkins, Bryan A.; Laverty, Sean M.

    2016-03-01

    Regulatory T cells (Tregs) have tremendous influence on treatment outcomes in patients receiving immunotherapy for cancerous tumors. We present a mathematical model incorporating the primary cellular and molecular components of antitumor laser immunotherapy. We explicitly model developmental classes of dendritic cells (DCs), cytotoxic T cells (CTLs), primary and metastatic tumor cells, and tumor antigen. Regulatory T cells have been shown to kill antigen presenting cells, to influence dendritic cell maturation and migration, to kill activated killer CTLs in the tumor microenvironment, and to influence CTL proliferation. Since Tregs affect explicitly modeled cells, but we do not explicitly model dynamics of Treg themselves, we use model parameters to analyze effects of Treg immunosuppressive activity. We will outline a systematic method for assigning clinical outcomes to model simulations and use this condition to associate simulated patient treatment outcome with Treg activity.

  1. The effect of a new communication template on anticipated willingness to initiate or resume allergen immunotherapy

    DEFF Research Database (Denmark)

    Calderon, Moises A; Cox, Linda; Casale, Thomas B; Mösges, Ralph; Pfaar, Oliver; Malling, Hans-Jørgen; Sastre, Joaquin; Khaitov, Musa; Demoly, Pascal

    2015-01-01

    BACKGROUND: A patient's knowledge of his/her allergic condition and treatment is a key factor in adherence and effectiveness. METHODS: To assess patients' understanding of allergy and acceptance of allergen immunotherapy on the basis of (i) information given by their physician at the time of...... prescription and (ii) a new communication template viewed some months later, we performed an Internet-based survey of patient panels in France, Germany, Spain, the USA and Russia. The survey participants were either recent "early abandoners" (having discontinued allergen immunotherapy before the end of the...... effectiveness (39 %) and complained about expense (39 %) and practical constraints (32 %). Twenty-two percent of the non-starters feared side effects. The communication template was considered to be clear (by 92 % of the patients), convincing (by 75 %) and reassuring (by 89 %); 80 % of the participants felt...

  2. Messenger RNA electroporation: an efficient tool in immunotherapy and stem cell research.

    Directory of Open Access Journals (Sweden)

    P Ponsaerts

    2005-12-01

    Full Text Available Over the last decades medicine has developed tremendously, but still many diseases are incurable. The last years, cellular (gene therapy has become a hot topic in biomedical research for the potential treatment of cancer, AIDS and diseases involving cell loss or degeneration. Here, we will focus on two major areas within cellular therapy, cellular immunotherapy and stem cell therapy, that could benefit from the introduction of neo-expressed genes through mRNA electroporation for basic research as well as for clinical applications. For cellular immunotherapy, we will provide a state-of-the-art on loading antigen-presenting cells with antigens in the mRNA format for manipulation of T cell immunity. In the area of stem cell research, we will highlight current gene transfer methods into adult and embryonic stem cells and discuss the use of mRNA electroporation for controlling guided differentiation of stem cells into specialized cell lineages.

  3. Cancer immunotherapy in clinical practice-the past, present, and future

    Institute of Scientific and Technical Information of China (English)

    Gaurav Goel; Weijing Sun

    2014-01-01

    Considerable progress has been made in the field of cancer immunotherapy in recent years. This has been made possible in large part by the identification of new immune-based cellular targets and the development of novel approaches aimed at stimulating the immune system. The role played by the immunosuppressive microenvironment in the development of tumors has been established. The success of checkpoint-inhibiting antibodies and cancer vaccines has marked the beginning of a new era in cancer treatment. This review highlights the clinically relevant principles of cancer immunology and various immunotherapeutic approaches that have either already entered mainstream oncologic practice or are currently in the process of being evaluated in clinical trials. Furthermore, the current barriers to the development of effective immunotherapies and the potential strategies of overcoming them are also discussed.

  4. Melittin-MIL-2 fusion protein as a candidate for cancer immunotherapy

    OpenAIRE

    Liu, Mingjun; Wang, Haitao; Liu, Linjie; Wang, Bin; Sun, Guirong

    2016-01-01

    Background Cytokine fusion protein that modulates the immune response holds great potential for cancer immunotherapy. IL-2 is an effective treatment against advanced cancers. However, the therapeutic efficacy of IL-2 is limited by severe systemic toxicity. Several mutants recombinant IL-2 can increase antitumor activity and minimize systemic toxicity. Melittin is an attractive anticancer candidate because of its wide-spectrum lytic properties. We previously generated a bifunctional fusion pro...

  5. Enhancing immunotherapy using chemotherapy and radiation to modify the tumor microenvironment

    OpenAIRE

    Kershaw, Michael H; Devaud, Christel; John, Liza B; Jennifer A Westwood; Darcy, Phillip K

    2013-01-01

    The tumor microenvironment is a complex assortment of cells that includes a variety of leukocytes. The overall effect of the microenvironment is to support the growth of tumors and suppress immune responses. Immunotherapy is a highly promising form of cancer treatment, but its efficacy can be severely compromised by an immunosuppressive tumor microenvironment. Chemotherapy and radiation treatment can mediate tumor reduction through cytotoxic effects, but it is becoming increasingly clear that...

  6. Penile tuberculosis following intravesical Bacille Calmette-Guérin immunotherapy

    OpenAIRE

    Chowdhury, Anadi Roy; Dey, Ranjan Kumar

    2013-01-01

    Bacille Calmette-Guérin (BCG) is an effective treatment for patients with superficial bladder cancer and bladder carcinoma in situ (CIS). It may cause side effects usually due to local and systemic inflammatory effects. We report a case of a male patient with non-invasive urothelial carcinoma of urinary bladder (Stage T1) who developed caseating granulomas on his glans penis as a complication of intravesical BCG immunotherapy. Though there are other reported cases of BCG dissemination noted i...

  7. Tumour Devitalization as a Tool for Cancer Immunotherapy Experiences from Animal Models

    Czech Academy of Sciences Publication Activity Database

    Horák, Vratislav; Vannucci, Luca; Morávková, Alena; Strnádel, Ján; Holubová, Monika; Hradecký, Jan; Klaudy, Jiří; Pokorná, Eva; Usvald, Dušan; Plánská, Daniela; Burócziová, Monika; Vure, Michal

    Indore: School of Biotechnology, 2009. s. 3-3. [5th World Congress of Cellular and Molecular Biology. 02.011.2009-06.11.2009, Indore] R&D Projects: GA MŠk 2B08063; GA ČR GA524/04/0102 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : Devitalization * Cancer immunotherapy * Melanoma -bearing Libechov Minipig Subject RIV: EC - Immunology

  8. Structural pathways of cytokines may illuminate their roles in regulation of cancer development and immunotherapy

    OpenAIRE

    Emine Guven-Maiorov; Saliha Ece Acuner-Ozbabacan; Ozlem Keskin; Attila Gursoy; Ruth Nussinov

    2014-01-01

    Cancers 2014, 6, 663-683; doi:10.3390/cancers6020663 cancers ISSN 2072-6694 www.mdpi.com/journal/cancers Review Structural Pathways of Cytokines May Illuminate Their Roles in Regulation of Cancer Development and Immunotherapy Emine Guven-Maiorov 1, Saliha Ece Acuner-Ozbabacan 1, Ozlem Keskin 1, Attila Gursoy 1 and Ruth Nussinov 2,3,* 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumelifeneri Yolu, 34450 Sariyer ...

  9. Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes

    OpenAIRE

    Bellin, Melena D.; Barton, Franca B.; Heitman, Andrew; Alejandro, Rodolfo; Hering, Bernhard J.

    2012-01-01

    The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has raised concern about its clinical utility. We hypothesized that induction immunosuppression therapy determines durability of insulin independence. We analyzed the proportion of insulin independent patients following final islet infusion in four groups of ITA recipients according to induction immunotherapy: University of Minnesota recipients given FcR nonbinding anti-CD3 antibody alone or T cell dep...

  10. Trends in Specific Immunotherapy for Allergic Rhinitis: A Survey of Chinese ENT Specialists

    OpenAIRE

    Zhou, Han; Tao, Qi-Lei; Wei, Jun-Min; Xu, Geng; Cheng, Lei

    2014-01-01

    Purpose Specific immunotherapy (SIT) is a suitable but uncommon treatment option for allergic rhinitis (AR) in China. The current understanding and attitude of Chinese ENT (ear, nose, and throat) specialists in regards to SIT is unclear. This study investigates current trends in the awareness and application status of SIT among Chinese ENT specialists. Methods We performed a nationwide, cross-sectional survey with a specially designed questionnaire given to 800 ENT specialists in China. A mem...

  11. IMMUNOTHERAPY WITH VISCUM ALBUM EXTRACT IN THE TREATMENT OF ADVANCED COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    T. Oniu

    2011-11-01

    Full Text Available Background: Most clinical trials using mistletoe to treat colorectal cancer are out-of-date and have major methodological weaknesses that raise doubts about their findings. Meanwhile, the arsenal of chemotherapy has much evolved over the last decade. Thus, the aim of this study was to determine the effectiveness of the total plant extract Isorel in association with modern chemotherapy in the treatment of colorectal cancer. Methods: After the surgical removal of the primary tumor, a total of 124 patients with advanced colorectal cancer (stage Dukes C and D, were randomly divided into the immunotherapy group (Isorel associated in most of the cases with chemotherapy, n=58 and the control group (most of which received chemotherapy. The chemotherapy regimens were based on 5-fluorouracil, irinotecan and oxaliplatin. Overall survival and adverse events were observed. Results: The addition of immunotherapy with Viscum album extract Isorel to 5FU-based chemotherapy significantly improved overall survival in Dukes stage C (5-year survival: 46% vs. 17%; median survival: 46 vs. 24 months, p=0.004 and D (median survival: 13,5 vs. 9,5 months, p=0.02; longest survival: 26 vs. 12 months. The addition of immunotherapy to oxaliplatin- and irinotecan-based chemotherapy further improved overall survival in Dukes stage C (5-year survival: 64% vs. 38%; median survival: 57,5 vs. 34 months, p=0.04 and D (median survival: 24 vs. 18 months, p=0.02; longest survival: 36 vs. 24 months. Inflammatory local reactions at the s.c. injection site occur frequently (83% of patients at the beginning of the treatment for 1 to 8 weeks. Conclusions: Immunotherapy with Viscum album extract Isorel, added to chemotherapy, improves the survival of the patients operated for advanced colorectal cancer compared with chemotherapy alone, whatever its type.

  12. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens

    OpenAIRE

    Cezmi A Akdis; Akdis, Mübeccel

    2015-01-01

    Substantial progress in understanding mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumors, organ transplantation and chronic infections has led to a variety of targeted therapeutic approaches. Allergen-specific immunotherapy (AIT) has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific way of treatment. The mechanisms by which allergen-AIT has its mechanisms of action include the very early d...

  13. Allergen specific immunotherapy: The future cure for allergic asthma. Mechanisms and improvement in a mouse model

    OpenAIRE

    Taher, Y.A.

    2007-01-01

    Allergic asthma is a disease characterized by persistent allergen-driven airway inflammation, remodeling and airway hyperresponsiveness (AHR). CD4+ T-cells, in particular T-helper type 2 (Th2) cells, play a critical role in orchestrating the disease process through the release of cytokines like IL-4, IL-5 and IL-13. Allergen-specific immunotherapy (IT) is currently the only disease-modifying treatment with long-term suppression of allergen-induced complaints. However, although IT is effective...

  14. Interferon-gamma Immunotherapy in a Patient With Refractory Disseminated Candidiasis.

    Science.gov (United States)

    Buddingh, Emilie P; Leentjens, Jenneke; van der Lugt, Jasper; Dik, Willem A; Gresnigt, Mark S; Netea, Mihai G; Pickkers, Peter; Driessen, Gertjan J

    2015-12-01

    Despite advances in supportive care and novel antifungal agents, mortality caused by invasive Candida infection is high. A 3-year-old boy with disseminated Candida dubliniensis infection during induction chemotherapy for acute lymphoblastic leukemia deteriorated despite resolution of neutropenia and appropriate antifungal treatment. Monocyte human leukocyte antigen-DR expression was extremely low, suggesting immunoparalysis. Adjuvant immunotherapy with interferon-gamma restored the immune response, which was accompanied by clinical and radiographic recovery. PMID:26379166

  15. IL-12 gene therapy for cancer: in synergy with other immunotherapies

    OpenAIRE

    Melero, I; Mazzolini, G; Narvaiza, I; Qian, C.; Chen, L.; Prieto, J

    2001-01-01

    In preclinical models of cancer, gene therapy with interleukin 12 (IL-12) has reached unprecedented levels of success when combined with immunotherapy approaches such as gene transfer of other cytokines and/or chemokines, costimulatory molecules or adoptive cell therapy. These combinations have been found to produce synergistic rather than additive effects. Meanwhile, IL-12 gene therapy is beginning clinical testing as a single agent, but combination strategies are at hand.

  16. Does Immunotherapy of Viral Warts Provide Beneficial Effects When It Is Combined with Conventional Therapy?

    OpenAIRE

    Choi, Jae Woo; Cho, Soyun; Lee, Jong Hee

    2011-01-01

    Background Cryotherapy has been accepted as the mainstay in treating periunugal and palmoplantar warts. The major drawback of cryotherapy is the requirement of several unbearably painful treatment sessions. Objective This study aims to assess the efficacy of immunotherapy in viral wart treatment, as an adjunctive method to cryotherapy. Methods Retrospective chart review was performed on 124 patients visiting the hospital from January to December 2009 for the treatment of periungual and planta...

  17. Bystander immunotherapy as a strategy to control allergen-driven airway inflammation.

    OpenAIRE

    Navarro, Séverine; Lazzari, Anne; Kanda, Akira; Fleury, Sébastien; Dombrowicz, David; Glaichenhaus, Nicolas; Julia, Valérie

    2014-01-01

    International audience Allergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), lung infiltration of Th2 cells, and high levels of IgE. To date, allergen-specific immunotherapy (SIT) is the only treatment that effectively alleviates clinical symptoms and has a long-term effect after termination. Unfortunately, SIT is unsuitable for plurisensitized patients, and highly immunogenic allergens cannot be used. To overcome these hurdles, we sought to i...

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

    OpenAIRE

    Delia Nelson; Scott Fisher; Bruce Robinson

    2014-01-01

    Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more “full frontal” treatment...

  19. Generation of hypoallergenic neoglycoconjugates for dendritic cell targeted vaccination: A novel tool for specific immunotherapy

    OpenAIRE

    Weinberger, Esther E.; Himly, Martin; Myschik, Julia; Hauser, Michael; Altmann, Friedrich; Isakovic, Almedina; Scheiblhofer, Sandra; Thalhamer, Josef; Weiss, Richard

    2013-01-01

    The incidence of allergic disorders and asthma continuously increased over the past decades, consuming a considerable proportion of the health care budget. Allergen-specific subcutaneous immunotherapy represents the only intervention treating the underlying causes of type I allergies, but still suffers from unwanted side effects and low compliance. There is an urgent need for novel approaches improving safety and efficacy of this therapy. In the present study we investigated carbohydrate-medi...

  20. Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

    OpenAIRE

    Klebanoff, Christopher A.; Khong, Hung T.; Antony, Paul A.; Douglas C Palmer; Restifo, Nicholas P

    2005-01-01

    Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine ‘sinks’ for homeostatic γC-cytoki...