Monoclonal antibodies and superantigens: a novel therapeutic approach

Abstract

We have developed a monoclonal antibody (mAb) based therapy intended for the treatment of solid tumors utilizing both main arms of the immune system by incorporating the colon carcinoma recognizing mAb C215 and the T cell activating bacterial staphylococcal enterotoxin A (SEA) in a single hybrid molecule. The recombinant tumor specific superantigen C215-SEA retained excellent antigen binding properties while the binding to MHC class II was markedly reduced and should allow targeting of a large fraction of T cells to tumors in vivo. C215-SEA mediated T cell killing of C215 expressing tumor cells irrespective of their expression of MHC class II antigens and induced levels of IFN-gamma and TNF in mononuclear cells sufficient to completely suppress the growth of colon carcinoma cells in vitro. In initial studies of anti-tumor effects, C215Fab-SEA was found to markedly inhibit the growth of colon carcinoma cells transplanted to Scid mice adoptively transferred with human mononuclear cells.