Induction of cytotoxicity in resting human T lymphocytes bound to tumor cells by antibody heteroconjugates.
An in vitro model for peripheral human T-cell activation and resultant tumor cell killing is described. Cytotoxic T lymphocytes may be generated from resting lymphocytes by incubation of human peripheral blood mononuclear cells for 3 days with the anti-CD3 monoclonal antibody OKT3. Cytotoxicity in peripheral blood mononuclear cells can also be induced by adding an anti-target-OKT3 antibody conjugate and 10% (vol/vol) fetal calf serum to the culture medium. Conjugate activation of T cells was almost completely blocked, however, when 20% (vol/vol) human serum was added to the medium. Conjugate-mediated peripheral blood mononuclear cells activation was restored to some extent by the addition of melanoma target cells to the culture and was markedly enhanced by a second conjugate containing anti-target cell and anti-CD28 antibody. Monoclonal antibody 9.3 (anti-CD28) provides a progression signal in T-lymphocyte activation when used in combination with anti-CD3. Thus, presentation by the tumor target cells of anti-CD3 and anti-CD28 to resting human lymphocytes causes T-cell activation, which is independent of monocytes, proceeds in the presence of human serum, and results in tumor cell killing.
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D003432:Cross-Linking Reagents