Anti-tumor immunity against CT26 colon tumor in mice immunized with plasmid DNA encoding beta-galactosidase fused to an envelope protein of endogenous retrovirus

Endogenous retroviral gene products have been recognized as being expressed in human cancerous tissues. However, these products have not been shown to be antigenic targets for T-cells, possibly due to immune tolerance. Since carcinogen-induced colon tumor CT26 expresses an envelope protein, gp70, of an endogenous ecotropic murine leukemia virus that is comparable to human tumor-associated antigens, we examined whether a DNA vaccine containing the gp70 gene induces protective immunity against CT26 cells. Injection of mic e with plasmid DNA (pDNA) encoding gp70 alone failed to induce anti-gp70 an tibody (Ab) or anti-CT26 cytotoxic T lymphocyte (CTL) responses. However, i mmunization with pDNA encoding the beta-galactosidase(beta-gal)/gp70 fusion protein induced anti-gp70 Ab and anti-CT26 CTL responses and conferred pro tective immunity against CT26 cells. These results indicate that beta-gal a cts as an immunogenic carrier protein that helps in the induction of immune responses against the poorly immunogenic gp70. Considering these results, it is possible that potential tolerance to the endogenous retroviral gene p roducts expressed by human tumors may be overcome by DNA vaccines that cont ain an endogenous retroviral gene fused to genes encoding immunogenic carri er proteins. (C) 2000 Academic Press.