Synergistic in vitro and in vivo anti-tumor effect of daunomycin-anti-96-kDa melanoma-associated antigen monoclonal antibody CL 207 conjugate and recombinant IFN-gamma.
The mAb CL 207 recognizes a 96-kDa melanoma-associated Ag. The latter is not modulated by antibody but is highly susceptible to induction by immune IFN-gamma on human carcinoma and melanoma cells. The mAb CL 207 does not mediate C- and cell-dependent lysis of human carcinoma and melanoma cells. Conjugation of daunomycin with mAb CL 207 causes a slight reduction of its immunoreactivity and affinity but does not affect its serologic specificity or the toxicity of daunomycin. In combination with IFN-gamma, the daunomycin-mAb CL 207 conjugate displays a selective in vitro and in vivo toxic effect on tumor cells that express the 96-kDa MAA. The synergistic effect of IFN-gamma and daunomycin-mAb CL 207 conjugate is specific. The in vivo toxicity is influenced by the interval between injection of human tumor cells into nude mice and that of IFN-gamma and daunomycin-mAb CL 207 conjugate. The present results suggest that the 96-kDa melanoma-associated Ag may be a useful model to investigate the combined use of IFN-gamma and mAb for the selective destruction of tumor cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000633:toxicity*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003630:Daunorubicin / Q000633:toxicity*; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity*; D007371:Interferon-gamma / Q000633:toxicity*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000633:toxicity
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000922:Immunotoxins; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D003630:Daunorubicin