High level antibody response to retrovirus-associated but not to melanocyte lineage-specific antigens in mice protected against B16 melanoma

Mice vaccinated with Mycobacterium tuberculosis Ag38 gene-transduced B16 me lanoma cells showed significant protection from intravenous challenge with parental B16 melanoma cells. No cytotoxic T-cell activity was found against melanoma cells, although the endogenous presence of the mycobacterial gene induced a preferential Th1 response. After immunization, a low serological response against melanoma cells was detected, while a high titer of antibo dies directed to parental B16 cells, mainly of IgG2(a) isotype, was found i n protected mice after challenge. These antibodies exhibited complement-dep endent cytotoxicity against melanoma cells in vitro, while in vivo, used in passive immunization, they induced a decrease in a number of experimental B16 lung metastases. Most of the antibodies were directed against endogenou s murine leukemia viruses. No reactivity against melanocyte lineage-specifi c antigens was observed. In particular, no reactivity was found in sera fro m protected mice against tyrosinase related protein 2 (TRP-2), either stabl y expressed in a non melanoma cell line or obtained by in vitro transcripti on-translation, or against tyrosinase, TRP-1 and gp 100 antigens immunoprec ipitated from B16 cells. Thus, in the B16 murine model, the presence of dom inant viral antigens induces a very strong humoral response that might be p rotective and may inhibit or mask the presence of minor clonotypes. (C) 199 9 Wiley-Liss, Inc.