Immunological results of a phase II randomized trial of multipeptide vaccines for melanoma

Abstract

7503 Background: To evaluate the immunogenicity of 12 peptides from cancer-testis and melanocyte differentiation proteins, and to assess the feasibility of complex peptide vaccines, a randomized phase II trial was performed in 51 patients with resected high-risk melanoma. Methods: Arm 1 received 4 peptides and arm 2 received 12 peptides. Each vaccine was an emulsion of 4 or 12 peptides (100ug each), a tetanus helper peptide (190ug), Montanide ISA-51 adjuvant (1 ml), and GM-CSF (110 ug). T-cell responses were evaluated in peripheral blood lymphocytes and in a sentinel immunized node by IFNγ ELIspot assay after one in vitro sensitization. Results: All patients have completed treatment; immunologic assessment is complete on 31 patients. Preliminary data from these 31 patients reveal immune responses in 11/14 patients (79%) on arm 1 and 17/17 patients (100%) on arm 2. Responses to 9 of the peptides are shown (Table). Patients on arm 2 responded to an average of 2.8 different peptides, those on arm 1 responded to an average of only 0.9 peptides. By comparing T cell responses to three index peptides in both peptide mixtures, it will be possible to assess whether co-administration of 4 peptides binding the same MHC molecule interferes with immunogenicity of the index peptides. Current results indicate that the median of the best immune responses for index peptides (fold-increase over background) was 9.7 in arm 1 and 11.1 in arm 2. The mean number of responses to index peptides per patient was 0.7 for Group 1, and 1.1 for Group 2. Conclusions: These findings support that (1) the most immunogenic peptides in this study were from tyrosinase, gp100, MAGE-A1, and MAGE-A10; (2) multiple peptides can be administered in combined aqueous mixture with safety and immunogenicity, and (3) immunogenicity is maintained despite peptide competition for binding to MHC. Further investigation of multiple-peptide vaccine mixtures is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration This was funded primarily by the NCI (R01 CA57653), but funding was provided by Immunex for purchase of GMCSF used in the vaccines