Adjuavnt tyrosinase peptide vaccination in patients with resected stage III/IV melanoma
2570 Background: This phase II study was undertaken to evaluate the immunogenicity and clinical efficacy of vaccination with tyrosinase peptides as adjuvant treatment in melanoma patients after multiple relapses. Methods: Stage III/IV melanoma patients after complete resection of relapses were vaccinated with tyrosinase peptides together with GM-CSF and KLH. Vaccination was given bi-weekly times 4, followed by monthly times 8 in absence of relevant disease progression. Tyrosinase-specific T cells were quantitated and characterized ex vivo by intracellular cytokine flow cytometry. Results: 44 patients were accrued with a median of 5.8 (range 2–25) previous relapses at cutaneous /s.c. only (n = 11), ln (n = 30) and/or visceral sites (n = 7). 11 patients received less than 6 vaccinations due to rapid progression. Of 32 patients evaluable for immunological response 16 (50%) displayed pre-vaccine spontaneous tyrosinase-specific T cells (median 0.32%). In 7 of the 15 patients without pre-existing T cells tyrosinase-specific T cells were induced after 6 vaccinations (median 0.08% CD3+CD8+ T cells) and in 10 of 12 patients after 12 vaccinations (median 0.36%, p = 0.03 compared to 6 vaccinations). Similarly, in 9 of the 16 patients with pre-existing T cell responses the frequency of tyrosinase-specific T cells did increase after 6 cycles (median 0.43 %), but in none of 10 patients with pre-existing T cells an increase was observed after 12 vaccinations (median 0.20%). Both, the spontaneous and the vaccine-induced T cells were predominantly of effector and effector-memory phenotype. With respect to clinical efficacy vaccination was terminated after 3 to 9 cycles due to disease progression in 19 of 44 patients. Of the remaining 25 patients receiving all 12 vaccinations 7 (16% of all 44 enrolled) had a favourable clinical course with cessation of recurrences. Conclusions: Taken together, this study shows high immunogenicity of the vaccine in patients with limited tumor burden associated with clinical efficacy. In case of a spontaneous pre-existing T cell response to the vaccine peptides, however, this could not, or only transiently be augmented. No significant financial relationships to disclose.