Production and Use of Anti-FcR Bispecific Antibodies

Bispecific antibodies (BsAb) are antibodies with two different specificities. BsAb composed of antl-FcγR Ab linked to anti-target Ab have been useful in exploring the function of the three classes of human FcγR. In addition, BsAb have been developed as new agents for immunotherapy which can join together different molecules or cells. In directed or redirected cytotoxicity, BsAb that bind both to target cells (pathogens or tumors) and to triggering molecules on leukocytes such as FcγR are used to focus normal cellular immune defense mechanisms specifically to the tumor cell or infectious agent. Limited clinical trials have demonstrated little toxicity and promising responses. This ability to redirect normal cytotoxic mechanisms to kill tumors, infectious agents, or infected cells makes BsAb powerful new therapeutic tools. In addition, BsAb are being used to target other appropriate molecules to FcγR, including antigens as vaccine adjuvants and immune complexes. This review focuses on BsAb in which one specificity is directed to FcγR on human leukocytes. It considers applications of these reagents and discusses the progress toward an understanding of the construction and use of BsAb in therapy.