Recognition of shared melanoma antigens in association with major HLA-A alleles by tumor infiltrating T lymphocytes from 123 patients with melanoma

A total of 123 tumor-infiltrating T lymphocyte (TIL) cultures established f rom patients with HLA-A1, -A2, -A3, -A24, or -A31 metastatic melanoma in th e Surgery Branch, National Cancer Institute, were screened for recognition of shared melanoma antigens including five melanosomal proteins (tyrosinase , MART-1/melan-A. gp100, TRP1, TRP2) as well as peptides derived from MAGE- 1 and MAGE-3. Examination of the specificity of these T cells indicated tha t 16% of HLA-A1 TIL, 57% of HLA-A2 TIL, 7% of HLA-A3 TIL, 13% of HLA-A24 TI L, and 27% of HLA-A31 TIL, recognized shared melanoma antigens restricted b y major histocompatibility complex class I. Melanosomal proteins were frequ ently recognized by these TIL, and MART-1(27-35), gp100(154-162), gp100(209 -217), and gp100(280-288) represent highly immunogenic epitopes that were r ecognized by a high percentage of HLA-A2 restricted melanoma reactive TIL. Recognition of gp100 by HLA-A2 restricted TIL significantly correlated with clinical response to adoptive immunotherapy with TIL in 21 HLA-A2 melanoma patients (p = 0.024). Four HLA-A1, two HLA-A2, two HLA-A3, one HLA-A24, an d two HLA-A31 restricted shared antigen-specific TIL did not recognize the previously identified antigens tested in this study, and may be useful for the identification of new melanoma antigens. The observation that TILs isol ated from patients with metastatic melanoma recognized melanosomal proteins in the context of predominant HLA-A alleles implies that it may be possibl e to develop immunotherapies for patients with melanoma expressing diverse HLA types.