Long‐term freedom from recurrence in 2 stage IV melanoma patients following vaccination with tyrosinase peptides

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Abstract
We report here on 2 patients who received adjuvant vaccination with an HLA‐A2– or HLA‐A24–restricted tyrosinase peptide, respectively, and GM‐CSF for frequently relapsing stage IV melanoma. Following resection of metastases and irradiation of brain metastases in 1 patient, both patients were without evidence of disease when receiving the first vaccination. While the patients had had 9 and 12, respectively, mostly s.c., relapses during the 3 years before vaccination, they experienced freedom from relapse for more than 2 years after vaccination. We found a T‐cell response to the vaccine peptide in both patients in the peripheral blood by ex vivo IFN‐γ ELISPOT assay. The T‐cell population could be further characterized by 4‐color flow cytometry in 1 patient, showing that the majority of the peptide‐specific CD3+CD8+IFN‐γ+ T cells were granzyme B‐positive and CCR‐7‐negative, characterizing them as effector T cells with the ability to mediate cytotoxicity and migrate to inflamed tissues. In this patient also, augmentation of the T‐cell response to autologous tumor cells by vaccination could be detected. A single‐site postvaccination relapse occurred in both patients, showing downregulation of tyrosinase expression in 1 patient, while normal expression levels for tyrosinase, MHC class I antigens and components of the antigen‐processing machinery were found in the other patient. These results suggest that peptide vaccination resulted in a prolonged relapse‐free interval in these high‐risk patients.

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