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-1 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.
Sfondrini
L
L
Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
Morelli
D
D
Bodini
A
A
Colnaghi
M I
MI
Ménard
S
S
Balsari
A
A
D016475:3T3 Cells; D000818:Animals; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology; D016466:CHO Cells; D019496:Cancer Vaccines / Q000276:immunology; D019070:Cell Lineage; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007109:Immunity; D007074:Immunoglobulin G / Q000276:immunology; D007370:Interferon Type I / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D009052:Leukemia Virus, Murine / Q000276:immunology; D008544:Melanocytes / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011233:Precipitin Tests; D011257:Pregnancy Proteins / Q000235:genetics; D012190:Retroviridae / Q000276:immunology*; D014161:Transduction, Genetic
D000956:Antigens, Viral; D019496:Cancer Vaccines; D018076:DNA, Complementary; D007074:Immunoglobulin G; D007370:Interferon Type I; D011257:Pregnancy Proteins; C020947:interferon tau; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase