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Immunologic hierarchy and promiscuity of melanoma helper peptides
© Hu et al; licensee BioMed Central Ltd. 2013
Published: 7 November 2013
Melanoma vaccines have been designed to expand specific CD8+ T-cells, but melanoma-reactive helper T-cells also can have antitumor activity. We previously observed clinical activity of a vaccine incorporating 6 melanoma helper peptides (6MHP), and found associations between CD4+ T cell response and survival. With the present study, in the spirit of personalized cancer immunotherapy, we define the relative immunogenicity and HLA allele promiscuity of individual helper peptides, and identify helper peptide-mediated augmentation of melanoma-specific CD8+ T-cell response.
Thirty-seven patients with stage IIIB-IV melanoma were vaccinated with 6MHP in incomplete Freund’s adjuvant. The vaccines contained 6 peptides: gp10044-59 (first 3 amino acids: WNR), Tyrosinase56-70 (AQN), Tyrosinase386-406 (FLL), Melan-A/MART-151-73 (RNG), MAGE-A3281-295 (TSY), and MAGE-A1, 2,3,6121-134 (LLK). Peripheral blood mononuclear cells (PBMC) and sentinel immunized nodes (SIN) were collected. CD4+ T-cell proliferation was assessed by thymidine uptake after exposure to peptides. CD8+ T-cell response was assessed by direct IFN-γ ELIspot assay against 14 MHC class I-restricted peptides.
The 6MHP vaccine has CD4+ T-cell immunogenicity beyond known HLA-DR restrictions. Patients whose tumors express tyrosinase, MAGE-A3, and several other MAGE proteins may be ideal for vaccination with 6MHP. The 4 most immunogenic peptides warrant further study, perhaps in combination immune therapies.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.