995 Genes coding for tumor rejection antigens

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We have isolated a number of genes that code for antigens recognized on human melanomas by autologous cytolytic T cells (CTL). A gene named MAGE-1 codes for two different antigenic peptides that are recognized by CTL on MHC molecules HLA-A1 and HLA-Cw16 respectively. This gene belongs to a family of 12 closely related genes. No expression of these genes was found on a large panel of normal tissues except for testis. The genes of the MAGE family are all located on the q terminal region of the X chromosome. The putative proteins produced by these genes present almost identical hydrophobicity patterns, suggesting that they exert the same function, but this function remains unknown. Gene MAGE-4 carries at least eight alternative first exons preceded by different promoters. The MAGE gene family may therefore ensure that the same function is placed under the control of nineteen different promoters, allowing for very specific spatial and temporal regulation. Gene MAGE-3 codes for a second antigen presented by HLA-A1. The relevant antigenic peptide is encoded by the MAGE-3 sequence that is homologous to the MAGE-1 sequence that also codes for an antigen presented by HLA-A1. Recently, another peptide that is encoded by MAGE-3 and binds to HLA-A2 has been found to be recognized by CTL. Two additional genes that code for tumor antigens and are expressed only in tumors and in testis have been isolated. These genes, named BAGE and GAGE, are unrelated to each other and to the MAGE family. MAGE, BAGE and GAGE are expressed in a significant proportion of tumors of different histological types, such as melanomas head and neck carcinomas, non small cell lung carcinomas and bladder tumors. They are not expressed in certain types of tumors such as leukemias. Genes coding for differentiation products, such as tyrosinase and Melan A in melanomas, also code for antigens recognized by autologous CTL.