RECOGNITION OF MULTIPLE EPITOPES IN THE HUMAN-MELANOMA ANTIGEN GP100 BY TUMOR-INFILTRATING T-LYMPHOCYTES ASSOCIATED WITH IN-VIVO TUMOR-REGRESSION

Four of ten HLA-A2-restricted melanoma specific CTL that were derived from tumor-infiltrating lymphocytes (TIL) and administered to patients recognized the gp100 melanoma Ag and nine of ten recognized the MART- 1 Ag. Adoptive transfer of the four gp 100-reactive CTL, but not the o ther TIL, resulted in tumor regression when infused into autologous pa tients along with IL-2. Tumor regression was thus correlated with the recognition of gp100 by the administered T cells (p = 0.0048). To iden tify the epitopes recognized by these four gp100-reactive CTL, 169 pep tides containing HLA-A2.1 binding motifs were synthesized and screened for their recognition by TIL using cytotoxicity and IFN-gamma release assays. Five gp100 epitopes (two for TIL620, three for TIL660, one fo r TIL1143, and two for TIL1200) were recognized by CTL derived from di fferent patients. Five of eight HLA-A2 binding melanoma epitopes (five gp100, one MART-1/Melan-A, two tyrosinase) had intermediate binding a ffinity to HLA-A2.1. These gp100 epitopes may be responsible for media ting tumor rejection in vivo and thus may be useful for the developmen t of immunotherapies for patients with melanoma.