Initial Trial of Bispecific Antibody-Mediated Immunotherapy of CD15-Bearing Tumors: Cytotoxicity of Human Tumor Cells Using a Bispecific Antibody Comprised of Anti-CD15 (MoAb PM81) and Anti-CD64/FcγRI (MoAb 32)

The high-affinity receptor for IgG, FcγRI, expressed on monocytes and interferon-γ (IFN-γ)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to FcγRI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specificities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-FeγRI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular...