The human melanoma cell line MZ2-MEL expresses several tumor antigens defined in vitro by autologous cytolytic T lymphocytes. One of these antigens, MZ2-E, has been identified as a nonapeptide encoded by the MAGE1 gene and presented at the tumor cell surface by the HLA-Al molecule. Gene MAGE1 belongs to a family of closely related genes. The MAGE genes are clustered within two distinct regions on chromosome X. MAGE1 to -12 are located in the q terminal region of the chromosome (Xq26-qter), while an additional member (MAGE-Xp) has been identified in the Xp21.3 locus. The MAGE gene family is silent in healthy adult tissues, with two important exceptions: testis, where all members but MAGE7 are expressed, and placenta, where transcripts for MAGE3 and -4 have been detected. In contrast, MAGE1, -2, -3, -4, -6, and -12 are frequently expressed at high levels in a significant proportion of tumors of various histological types, including melanomas, colon carcinomas, leukemias, lung cancers, sarcomas, and breast cancers. In addition to the peptide corresponding to antigen MZ2-E, an additional peptide derived from MAGE1 and a peptide derived from MAGE3 have recently been identified as tumor antigens recognized by autologous cytolytic T cells. The MAGE proteins aremore » therefore considered to be attractive targets for cancer immunotherapy. However, it remains to be demonstrated that such a therapy will not affect tissues, like testis, where the corresponding genes are expressed. 15 refs., 3 figs.« less