GENES-CODING FOR TUMOR-ANTIGENS RECOGNIZED BY HUMAN CYTOLYTIC T-LYMPHOCYTES

In order to define the antigens recognized by cytolytic T lymphocytes (CTLs) on autologous tumors, we derived tumor-specific CTL clones from autologous mixed lymphocyte tumor cell cultures. The gene coding for a tumor rejection antigen expressed on a melanoma was isolated by tran sfecting genomic DNA of the tumor into an antigen-loss variant of the melanoma. Transfectants were identified on the basis of their ability to stimulate tumor necrosis factor release by the CTL clone. The gene that transferred the expression of the antigen was named MAGE-1. It is a new gene, silent in normal tissues with the exception of testis, bu t expressed in several types of tumors. The antigen recognized by the CTL clone is a nonapeptide derived from the protein encoded by gene MA GE-1, and presented by the HLA class I molecule HLA-A1. Using two othe r antimelanoma CTL clones, we identified the tyrosinase gene as coding for an antigen presented by HLA-A2 on this type of tumors. The identi fication of these tumor rejection antigens open new possibilities for the specific immunotherapy of cancer.