MELANOCYTE LINEAGE-SPECIFIC ANTIGEN GP100 IS RECOGNIZED BY MELANOMA-DERIVED TUMOR-INFILTRATING LYMPHOCYTES

We recently isolated a cDNA clone that encodes the melanocyte lineage- specific antigen glycoprotein (gp)100. Antibodies directed against gp1 00 are an important tool in the diagnosis of human melanoma. Since the gp100 antigen is highly expressed in melanocytic cells, we investigat ed whether this antigen might serve as a target for antimelanoma cytot oxic T lymphocytes (CTL). Here, we demonstrate that cytotoxic tumor-in filtrating lymphocytes (TIL) derived from a melanoma patient (TIL 1200 ) are directed against gp100. HLA-A2.1(+) melanoma cells are lysed by TIL from this patient. In addition, murine double transfectants, expre ssing both HLA-A2.1 and gp100, are lysed by TIL 1200, whereas transfec tants expressing only HLA-A2.1 are not susceptible to lysis. Furthermo re, the HLA-A2.1(+) melanoma cell line BLM, which lacks gp100 expressi on and is resistant to lysis, becomes susceptible after transfection o f gp100 cDNA. Finally, HLA-A2.1(+) normal melanocytes are lysed by TIL 1200. These data demonstrate that the melanocyte differentiation anti gen gp100 can be recognized in the context of HLA-A2.1 by CTL from a m elanoma patient. Gp100 may therefore constitute a useful target for sp ecific immunotherapy against melanoma, provided that no unacceptable c ytotoxicity towards normal tissue is observed.