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A Randomized Phase IITrial of MultiepitopeVaccination withMelanoma Peptides forCytotoxic T Cells andHelper T Cells forPatients withMetastatic Melanoma… Craig L. SlingluffCharles LeeFengmin Zhao2013 год

A Randomized Phase II Trial of Multiepitope Vaccination with Melanoma Peptides for Cytotoxic T Cells and Helper T Cells for Patients with Metastatic Melanoma (E1602)
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Аннотация: Abstract Purpose: This multicenter randomized trial was designed to evaluate whether melanoma helper peptides augment cytotoxic T lymphocyte (CTL) responses to a melanoma vaccine and improve clinical outcome in patients with advanced melanoma. Experimental Design: One hundred seventy-five patients with measurable stage IV melanoma were enrolled into 4 treatment groups, vaccinated with 12 MHC class I-restricted melanoma peptides to stimulate CTL (12MP, group A), plus a tetanus peptide (group B), or a mixture of 6 melanoma helper peptides (6MHP, group C) to stimulate helper T lymphocytes (HTL), or with 6 melanoma helper peptide (6MHP) alone (group D), in incomplete Freund's adjuvant plus granulocyte macrophage colony-stimulating factor. CTL responses were assessed using an in vitro-stimulated IFN-γ ELIspot assay, and HTL responses were assessed using a proliferation assay. Results: In groups A to D, respectively, CTL response rates to 12 melanoma peptides were 43%, 47%, 28%, and 5%, and HTL response rates to 6MHP were in 3%, 0%, 40%, and 41%. Best clinical response was partial response in 7 of 148 evaluable patients (4.7%) without significant difference among study arms. Median overall survival (OS) was 11.8 months. Immune response to 6 MHP was significantly associated with both clinical response (P = 0.036) and OS (P = 0.004). Conclusion: Each vaccine regimen was immunogenic, but MHPs did not augment CTL responses to 12 melanoma peptides. The association of survival and immune response to 6MHP supports further investigation of helper peptide vaccines. For patients with advanced melanoma, multipeptide vaccines should be studied in combination with other potentially synergistic active therapies. Clin Cancer Res; 19(15); 4228–38. ©2013 AACR.
Год издания: 2013
Авторы: Craig L. Slingluff, Charles Lee, Fengmin Zhao, Kimberly A. Chianese‐Bullock, Walter C. Olson, Lisa H. Butterfield, Theresa L. Whiteside, Philip D. Leming, John M. Kirkwood
Издательство: American Association for Cancer Research
Источник: Clinical Cancer Research
Ключевые слова: Immunotherapy and Immune Responses, vaccines and immunoinformatics approaches, Cancer Immunotherapy and Biomarkers
Другие ссылки: Clinical Cancer Research (HTML)
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