Clonal expansion of Melan A-specific cytotoxic T lymphocytes in a melanomapatient responding to continued immunization with melanoma-associated peptides

Peptides derived from human tumor antigens have been used in a number of cl inical trials to induce specific immune responses against autologous tumors in cancer patients. Although favorable clinical results were observed in s ingle patients, immune responses correlating with tumor regression were eit her not detected or in case of responses, the T-cell specificity was diffic ult to demonstrate. In this study, we analyzed antigen-specific T-cell resp onses induced in the skin and in peripheral blood lymphocytes (PBL) in an H LA-A2-positive melanoma patient. The patient showed major regression of met astatic melanoma under continued immunization with peptides derived from th e melanocyte differentiation antigens Melan A/MART-1, tyrosinase and gp100/ Pme117. Based on the identification of different T-cell receptor (TCR) fami lies reactive with Melan A/MART-1, we have demonstrated that i.d. immunizat ion with peptides alone leads to oligoclonal expansion of Melan A/MART-1-sp ecific cytotoxic T lymphocytes (CTL), detectable in local delayed-type hype rsensitivity (DTH) reactions and PBL. A monoclonal expansion of a Melan A/M ART-1-specific TCR VB 16 CTL was reproducibly observed after in vitro stimu lation with Melan A/MART-1 peptides. The same TCR VB 16 CTL clone was detec ted in skin biopsies taken from vitiligo areas. Our findings provide strong evidence for the effective induction of specific T-cell responses to Melan A/MART-1 by i.d. immunization with peptide alone, which accounts for derma l depigmentation, specific cytotoxicity against Melan A/MART-1-expressing m elanoma cells and clinical tumor regression. Int. J. Cancer 86:538-547, 200 0. (C) 2000 Wiley-Liss, Inc.