In vivo tumor immunotherapy by a bacterial superantigen.

Abstract

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.