Limited Induction of Tumor Cross-Reactive T Cells without a Measurable Clinical Benefit in Early Melanoma Patients Vaccinated with Human Leukocyte Antigen Class I–Modified Peptides
| العنوان: | Limited Induction of Tumor Cross-Reactive T Cells without a Measurable Clinical Benefit in Early Melanoma Patients Vaccinated with Human Leukocyte Antigen Class I–Modified Peptides |
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| المؤلفون: | Chiara Castelli, Marco Asioli, Paola Filipazzi, Claudia Lombardo, Michele Maio, Antonello Villa, Chiara Camisaschi, Riccardo Danielli, Gabrina Tragni, Gloria Sovena, Paola Frati, Gianluigi Rigamonti, Roberto Patuzzo, Licia Rivoltini, Paola Squarcina, Andrea Maurichi, Giorgio Parmiani, Agata Cova, Luigi Mariani, Felicetta Giardino, Annabella Di Florio, Lorenzo Pilla, Mario Santinami, Vanna Chiarion-Sileni |
| المساهمون: | Filipazzi, P, Pilla, L, Mariani, L, Patuzzo, R, Castelli, C, Camisaschi, C, Maurichi, A, Cova, A, Rigamonti, G, Giardino, F, Di Florio, A, Asioli, M, Frati, P, Sovena, G, Squarcina, P, Maio, M, Danielli, R, Chiarion Sileni, V, Villa, A, Lombardo, C, Tragni, G, Santinami, M, Parmiani, G, Rivoltini, L |
| المصدر: | Clinical Cancer Research. 18:6485-6496 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cancer Research, T-Lymphocytes, medicine.medical_treatment, Epitopes, T-Lymphocyte, Human leukocyte antigen, Cross Reactions, Cancer Vaccines, MART-1 Antigen, Immune system, medicine, Humans, Melanoma, Neoplasm Staging, business.industry, Histocompatibility Antigens Class I, Cancer, tumor recognition, medicine.disease, Vaccination, Treatment Outcome, Oncology, Immunization, Case-Control Studies, Vaccines, Subunit, Immunology, Peptides, business, Immunologic Memory, Adjuvant, CD8 |
| الوصف: | Purpose: The progressive immune dysfunctions that occur in patients with advanced melanoma make them unlikely to efficiently respond to cancer vaccines. A multicenter randomized phase II trial was conducted to test whether immunization with modified HLA class I tumor peptides in the context of adjuvant therapy results in better immunologic responses and improved clinical outcomes in patients with early melanoma (stages IIB/C-III). Experimental Design: Forty-three patients were enrolled to undergo vaccination (n = 22) or observation (n = 21). The vaccine included four HLA-A*0201–restricted modified peptides (Melan-A/MART-1[27L], gp100[210M], NY-ESO-1[165V], and Survivin[97M]) emulsified in Montanide ISA51 and injected subcutaneously in combination with cyclophosphamide (300 mg/m2) and low-dose IL-2 (3 × 106 IU). The immune responses were monitored using ex vivo IFN-γ–ELISpot, HLA/multimer staining, and in vitro short-term peptide sensitization assays. Results: Vaccination induced a rapid and persistent increase in specific effector memory CD8+ T cells in 75% of the patients. However, this immunization was not associated with any significant increase in disease-free or overall survival as compared with the observation group. An extensive immunologic analysis revealed a significantly reduced cross-recognition of the corresponding native peptides and, most importantly, a limited ability to react to melanoma cells. Conclusions: Adjuvant setting is an appealing approach for testing cancer vaccines because specific CD8+ T cells can be efficiently induced in most vaccinated patients. However, the marginal antitumor activity of the T cells induced by modified peptides in this study largely accounts for the observed lack of benefit of vaccination. These findings suggest reconsidering this immunization strategy, particularly in early disease. Clin Cancer Res; 18(23); 6485–96. ©2012 AACR. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d3c5b9ae8349137943b5dd0914a43af7Test https://doi.org/10.1158/1078-0432.ccr-12-1516Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d3c5b9ae8349137943b5dd0914a43af7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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