Immunization with a combination
melanoma helper
peptide (6MHP)
vaccine has been shown to induce CD4(+) T cell responses, which are associated with patient survival. In the present study, we define the relative immunogenicity and HLA allele promiscuity of individual helper
peptides and identify helper
peptide-mediated augmentation of specific CD8(+) T cell responses. Thirty-seven participants with stage IIIB-IV
melanoma were vaccinated with 6MHP in
incomplete Freund's adjuvant. The 6MHP
vaccine is comprised of 6
peptides representing melanocytic differentiation
proteins gp100,
tyrosinase,
Melan-A/MART-1, and
cancer testis antigens from the MAGE family. CD4(+) and CD8(+) T cell responses were assessed in peripheral blood and in sentinel immunized nodes (SIN) by
thymidine uptake after exposure to helper
peptides and by direct
interferon-γ ELIspot assay against 14 MHC class I-restricted
peptides.
Vaccine-induced CD4(+) T cell responses to individual
epitopes were detected in the SIN of 63 % (22/35) and in the peripheral blood of 38 % (14/37) of participants for an overall response rate of 65 % (24/37). The most frequently immunogenic
peptides were MAGE-A3281-295 (49 %) and tyrosinase386-406 (32 %). Responses were not limited to HLA restrictions originally described.
Vaccine-associated CD8(+) T cell responses against class I-restricted
peptides were observed in 45 % (5/11) of evaluable participants. The 6MHP
vaccine induces both CD4(+) and CD8(+) T cell responses against
melanoma antigens. CD4(+) T cell responses were detected beyond reported
HLA-DR restrictions. Induction of CD8(+) T cell responses suggests
epitope spreading and systemic activity mediated at the
tumor site.