Monoclonal antibodies and superantigens: A novel therapeutic approach

We have developed a monoclonai antibody (mAb) based therapy intended forthe treatment ofsolid 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 tumorsin vivo. C215-SEA mediated T cell killing of C215 expressing tumor cells irrespective of their expression of MHC class [I antigens and induced levels of IFN-y and TNF in mononuclear cells sufficient to completely suppress the growth of colon carcinoma cellsin 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 mononulear cells.