BINDING AND CYTOTOXICITY CHARACTERISTICS OF THE BISPECIFIC MURINE MONOCLONAL ANTIBODY-2B1

Bispecific monoclonal antibodies (BsmAb) with specificity for tumor Ag and effect or cell trigger molecules have been shown to redirect the cytotoxicity of several peripheral blood mononuclear cell populations against relevant tumor. The BsmAb, 2B1, binds to the extracellular dom ain of the c-erbB-2 gene product of the HER2/neu proto-oncogene and to CD16. In this report, the binding and cytotoxic characteristics of 2B 1 are presented. Maximal saturation binding of 2B1 to PBL and c-erbB-2 expressing SK-OV-3 cells occurred in the 1 mug/ml concentration range . However, substantial lysis potentiation was observed at 1000-fold lo wer BsmAb concentrations. Optimal tumor lysis was obtained when the Bs mAb, PBL, and target cells were continuously coincubated. When PBL wer e franked with 2B1, washed, and added to labeled targets, substantiall y less lysis was observed. These results suggest that the best way to therapeutically exploit the cytotoxic attributes of 2B1 may be to obta in continuous BsmAb exposure to tumor. Approaches based on franking of this BsmAb to PBL may not be warranted.