Immune interferon modulation of in vitro murine anti-human T cell monoclonal antibody-mediated cytotoxicity.
Limited antitumor effects have been achieved in clinical trials with murine monoclonal antibody T101, perhaps because of its limited ability to effect complement-mediated or cell-mediated cytotoxicity. We explored the effects of recombinant immune interferon on T101-mediated cytotoxicity in vitro. Interferon failed to enhance expression of the antigen detected by T101 on target cells, but it did increase Fc receptor binding of T101 and other IgG2A and IgG3 murine proteins, but not IgG1 or IgG2B. Preincubation of U937, HL60, and human mononuclear cells with 100 U of immune interferon for 48 hr, while T101 was preincubated with various T cell line targets or human CLL cells at 4 degrees C for 30 min before combining effectors and targets for 4 hr at 37 degrees C, resulted in cytotoxicity of 18 to 44% of maximum. Cytotoxicity in the absence of interferon or T101 was less than 5%. Unfortunately, rapid modulation of antigen-antibody when T101 was preincubated with targets at 37 degrees C prevented any increase in cytotoxicity under those conditions. We conclude that immune interferon can augment T101-mediated cytotoxicity in vitro, but it is unlikely that it would enhance T101-mediated cytotoxicity via complement or cell-mediated mechanisms in vivo.
Dillman
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Johnson
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Shawler
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D011961:Receptors, Fc / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D011961:Receptors, Fc; D007371:Interferon-gamma