Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immuno-gene therapy.
Two genes encoding human melanoma antigens MART-1 and gp100 recognized by HLA-A2 restricted melanoma reactive CTL derived from tumor infiltrating lymphocytes (TIL) were isolated by cDNA expression cloning methods. Multiple unmutated self peptides were identified as T cell epitopes in these melanocyte/melanoma specific proteins (2 from MART-1 and 5 from gp100). Most of these melanoma epitopes contain non-dominant anchor amino acids at the primary anchor positions and have intermediate binding affinity to HLA-A2.1. Melanoma reactive CTL were efficiently induced from PBL and TIL of patients by in vitro stimulation with PBMC pulsed with these epitopes. There is a significant correlation between vitiligo development and clinical response to IL2 based immunotherapy, suggesting that autoreactive T cells are involved in melanoma regression in vivo. These results have implications for understanding the nature of tumor antigens recognized by T cells and for the development of new cancer immunotherapies.
Kawakami
Y
Y
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Rosenberg
S A
SA
D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D006801:Humans; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014614:Vaccines, Synthetic