CLONING OF A NEW GENE ENCODING AN ANTIGEN RECOGNIZED BY MELANOMA-SPECIFIC HLA-A24-RESTRICTED TUMOR-INFILTRATING LYMPHOCYTES

The role of tumor-specific T cells in mediating the regression of meta static melanoma has been suggested by the clinical response of patient s to treatment with tumor-infiltrating lymphocytes (TIL). A number of Ags recognized by class I-restricted melanoma-specific T cells have re cently been isolated, raising the hope that this will lead to the deve lopment of improved therapies. In this study, we report the cloning of a tumor Ag recognized by T cells from melanoma patient 888. Previousl y, we reported that TIL 888, grown from the tumor of this patient, rec ognized tyrosinase in an HLA-A24-restricted fashion. This line, when i nfused into the autologous patient, resulted in complete regression of multiple metastases. Three years later, a second TIL line, TIL 1290, was isolated from a recurrent pelvic tumor. Infusion of a mixture of T IL 888 and TIL 1290 cell lines into the patient resulted in complete r egression of a residual abdominal mass and the patient remains disease -free 2 yr later. The TIL 1290 cell line, which recognized melanoma in an HLA-A24-restricted manner, failed to recognize tyrosinase. TIL 129 0 was then used to screen an 888 melanoma cDNA library, and an Ag was isolated that did not correspond to any found in sequence databases. T his gene, termed p15, was found to be expressed in a variety of normal tissues, and a peptide epitope recognized by TIL 1290 was found to re present the product of an nonmutated gene. Screening of additional cDN A pools resulted in the isolation of a second clone which stimulated T IL 1290. This clone also appeared to represent a transcript of the p15 gene, indicating that this gene may encode the predominant Ag recogni zed by TIL 1290.