Serological analysis of BALB/c methylcholanthrene sarcoma Meth A by SEREX:Identification of a cancer/testis antigen

Antigens of BALB/c methylcholanthrene-induced fibrosarcoma Meth A recognize d by the host humoral immune response were investigated by serological anal ysis of antigens by recombinant expression cloning (SEREX). Immunoscreening a cDNA library from Meth A (K gamma) cells (Meth A retrovirally transfecte d with murine IFN-gamma cDNA) with sera from BALB/c mice growing parental M eth A transplants identified 10 antigens. One of them, OY-MS-4, showed char acteristics of a cancer/testis (CT) antigen. Nucleotide sequence analysis r evealed that OY-MS-4 was identical to a mouse placenta and embryonic expres sion gene (pem) known to be selectively expressed during embryogenesis and in transformed cell lines. In adult mice, expression of OY-MS-4 war restric ted to testis and placenta. Four of 6 methylcholanthrene-induced fibrosarco mas in BALB/c mice showed strong expression of OY-MS-4. In 6 T-cell leukemi as, only a dimethylbenzanthracene-induced leukemia, EL4 (C57BL), showed str ong expression. Two other tumors, A20.2J and P815, induced by ethylnitrosou rea and methylcholanthrene, respectively, also strongly expressed OY-MS-4. The other 9 gene products identified in Meth A by SEREX were expressed in a ll 15 tumors tested and in a range of normal tissues. Sequence analysis of cDNA inserts coding for the SEREX-defined antigens showed no evidence of mu tation. Despite the expression of OY-MS-1-10 antigens in methyl-cholanthren e sarcomas other than Meth A, no antibody was detected in the sera of mice bearing these other sarcomas, The basis for the unique immunogenicity of OY -MS-1-10 presented by Meth A, but not by other syngeneic tumors expressing these gene products, is unknown. Int. J. Cancer 88: 845-851, 2000. (C) 2000 Wiley-Liss, Inc.