Induction of HLA-DP4–Restricted Anti-Survivin Th1 and Th2 Responses Using an Artificial Antigen-Presenting Cell
| العنوان: | Induction of HLA-DP4–Restricted Anti-Survivin Th1 and Th2 Responses Using an Artificial Antigen-Presenting Cell |
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| المؤلفون: | Marcus O. Butler, Lee M. Nadler, Sascha Ansén, Makito Tanaka, Alla Berezovskaya, Naoto Hirano, Osamu Imataki |
| المصدر: | Clinical Cancer Research. 17:5392-5401 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Cancer Research, Survivin, medicine.medical_treatment, Blotting, Western, Molecular Sequence Data, Antigen-Presenting Cells, Epitopes, T-Lymphocyte, Immunoglobulins, Human leukocyte antigen, CD8-Positive T-Lymphocytes, Major histocompatibility complex, Article, Inhibitor of Apoptosis Proteins, Viral Matrix Proteins, Interferon-gamma, Th2 Cells, Antigen, Cancer immunotherapy, Antigens, CD, Neoplasms, medicine, Humans, Amino Acid Sequence, Antigen-presenting cell, Alleles, HLA-DP beta-Chains, Membrane Glycoproteins, biology, Immunotherapy, Th1 Cells, Flow Cytometry, Phosphoproteins, Oncology, Immunology, B7-1 Antigen, biology.protein, Interleukin-4, Cancer vaccine, K562 Cells, CD80 |
| الوصف: | Purpose: In previous cancer vaccine clinical trials targeting survivin, induction of specific CD8+ T-cell responses did not consistently lead to clinical responses. Considering the critical role of CD4+ T-cell help in generating antitumor immunity, integration of anti-survivin CD4+ T-cell responses may enhance the efficacy of anti-survivin cancer immunotherapy. Human leukocyte antigen (HLA)-DP4 is emerging as an attractive MHC target allele of CD4+ T cell-mediated immunotherapy, because it is one of the most frequent HLA alleles in many ethnic groups. In this article, we aimed to elucidate DP4-restricted CD4+ T-cell responses against survivin in cancer patients. Experimental Design: We generated a human cell-based artificial antigen-presenting cell (aAPC) expressing HLA-DP4, CD80, and CD83 and induced DP4-restricted antigen-specific CD4+ T cells. The number, phenotype, effector function, and in vitro longevity of generated CD4+ T cells were determined. Results: We first determined previously unknown DP4-restricted CD4+ T-cell epitopes derived from cytomegalovirus pp65, to which sustained Th1-biased recall responses were induced in vitro by using DP4-aAPC. In contrast, DP4-aAPC induced in vitro both Th1 and Th2 long-lived anti-survivin CD4+ T cells from cancer patients. Both survivin-specific Th1 and Th2 cells were able to recognize survivin-expressing tumors in a DP4-restricted manner. Neither survivin-specific interleukin 10 secreting Tr1 cells nor Th17 cells were induced by DP4-aAPC. Conclusions: DP4-restricted anti-survivin Th1 and Th2 immunity with sufficient functional avidity can be induced from cancer patients. The development of strategies to concurrently induce both CD4+ and CD8+ T-cell responses against survivin is warranted for optimal anti-survivin cancer immunotherapy. Clin Cancer Res; 17(16); 5392–401. ©2011 AACR. |
| تدمد: | 1557-3265 1078-0432 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::947aa1dc72d69989c0926d90013ac3e7 https://doi.org/10.1158/1078-0432.ccr-10-3083 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....947aa1dc72d69989c0926d90013ac3e7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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