Tumor Specific Antigens

This category of tumor antigens, which represents non-mutated gene products that are not processed and presented on normal adult tissues, is predominantly comprised of members of the cancer/testis (C/T) family of genes (Table 2). The expression of C/T gene products is limited in adult tissues to the normal testis, which lacks expression of HLA class I and class II molecules. The prototype for this family, MAGE-1, represents the first antigen to be identified as a target of human tumor reactive T cells, and was cloned by transfecting an autologous tumor cell line that appeared to have lost antigen expression with a cosmid library containing genomic DNA from antigen positive tumor cells (1). The cancer/testis genes have been clustered into 10 families, 6 of which have been mapped to the X chromosome (3 8), and subsequent studies have lead to the identification of T cell epitopes expressed on multiple products derived from these gene families. The MAGE gene family includes 17 members, but additional families appear to contain only a small number of sequences, as the NY-ESO-1 families contains only 2 genes very closely related genes, NY-ESO-1 and LAGE-1. Members of these families are expressed at frequencies of up to 60% in melanoma, breast, lung, bladder and prostate cancers. Two epitopes recognized in the context of HLA-A1 have been identified from homologous regions of the MAGE-A1 and MAGE-A3 antigens (39). A reverse immunology approach was also used to identify an HLA-A2 restricted epitope of MAGE-A3 (40). This epitope may not generally be processed endogenously at levels sufficient to lead to T cell recognition, however, as

Table 2. HLA class I restricted differentiation antigens.

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