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 melanoma 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 antibodies directed to parental B16 cells, mainly of IgG2(a) isotype, was found in protected mice after challenge. These antibodies exhibited complement-dependent 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 endogenous murine leukemia viruses. No reactivity against melanocyte lineage-specific antigens was observed. In particular, no reactivity was found in sera from protected mice against tyrosinase-related protein 2 (TRP- 2), either stably expressed in a non-melanoma cell line or obtained by in vitro transcription-translation, or against tyrosinase, TRP-I and gp100 antigens immunoprecipitated from B16 cells. Thus, in the B16 murine model, the presence of dominant viral antigens induces a very strong humoral response that might be protective and may inhibit or mask the presence of minor clonotypes.