In vivo tumor immunotherapy by a bacterial superantigen.
We have investigated the in vivo efficacy of Staphylococcus aureus enterotoxin B (SEB) coupled to tumor-specific anti-idiotypic antibody in redirecting T cell effector activity to the growth inhibition of B lymphoma 38C13. Incubation of 38C13 lymphoma cells with syngeneic C3H/He splenic cells and SEB-anti-Id conjugate was associated with between 80 and 100% growth inhibition of the tumor cells. V beta 8+ T cells were integral for the SEB-anti-Id-induced tumor cell growth inhibition. Administration of SEB-anti-Id i.v. to mice previously inoculated with 38C13 lymphoma cells led to greater than 40% survival at 100 days compared to a mean survival of 21 days in control animals. When we compared this reagent with other targeting constructs--the anti-CD3-anti-Id and anti-TCR V beta 8-anti-Id--these more or less effectively prevented tumor growth. However, anti-CD3-anti-Id impaired almost the entire T cell response, whereas the effects of SEB-anti-Id or anti-V beta 8-anti-Id had effects limited to V beta 8+ T cells. Previous studies showed that in vivo administration of SEB caused a small change in V beta 8+ T cell numbers in contrast to anti-V beta 8 antibody, which depleted the entire population. These results together suggest that SEB-anti-tumor antibody conjugates represent a potentially powerful approach for better tumor immunotherapy.
Department of Immunology, University of Toronto, Ontario, Canada.
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Ochi
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Migita
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Xu
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Siminovitch
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D007167:Immunotherapy; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D000942:Antigens, Bacterial; D017252:CD3 Complex; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C031818:enterotoxin B, staphylococcal