IDENTIFICATION OF MULTIPLE CANCER TESTIS ANTIGENS BY ALLOGENEIC ANTIBODY SCREENING OF A MELANOMA CELL-LINE LIBRARY/

Cancer/testis (CT) antigens-immunogenic protein antigens that are expr essed in testis and a proportion of diverse human cancer types-are pro mising targets for cancer vaccines. To identify new CT antigens, we co nstructed an expression cDNA library from a melanoma cell line that ex presses a wide range of CT antigens and screened the library with an a llogeneic melanoma patient serum known to contain antibodies against t wo CT antigens, MAGE-1 and NY-ESO-1. cDNA clones isolated from this li brary identified four CT antigen genes: MAGE-4a, NY-ESO-1, LAGE-1, and CT7. Of these four, only MAGE-4a and NY-ESO-1 proteins had been shown to be immunogenic, LAGE-1 is a member of the NY-ESO-1 gene family, an d CT7 is a newly defined gene with partial sequence homology to the MA GE family at its carboxyl terminus, The predicted CT7 protein, however , contains a distinct repetitive sequence at the 5' end and is much la rger than MAGE proteins. Our findings document the immunogenicity of L AGE-1 and CT7 and emphasize the power of serological analysis of cDNA expression libraries in identifying new human tumor antigens.