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 expressed in testis and a proportion of diverse human cancer types-are promising targets for cancer vaccines. To identify new CT antigens, we constructed an expression cDNA library from a melanoma cell line that expresses a wide range of CT antigens and screened the library with an allogeneic melanoma patient serum known to contain antibodies against two CT antigens, MAGE-1 and NY-ESO-1. cDNA clones isolated from this library 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, and CT7 is a newly defined gene with partial sequence homology to the MAGE family at its carboxyl terminus. The predicted CT7 protein, however, contains a distinct repetitive sequence at the 5' end and is much larger than MAGE proteins. Our findings document the immunogenicity of LAGE-1 and CT7 and emphasize the power of serological analysis of cDNA expression libraries in identifying new human tumor antigens.
Chen
Y T
YT
Cornell University Medical College, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. ytchen@mail.med.cornell.edu
Güre
A O
AO
Tsang
S
S
Stockert
E
E
Jäger
E
E
Knuth
A
A
Old
L J
LJ
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D015723:Gene Library; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D013737:Testis / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000941:Antigens; D000951:Antigens, Neoplasm; D018076:DNA, Complementary