[Bispecific antibodies: what future?]

Abstract

Monoclonal antibodies have emerged as a very successful class of therapeutic agents. In their native format, monoclonal antibodies are monospecific in that they recognize only one epitope, but their Fc domain also binds to FcfR-expressing cells. Attempts to improve the cytotoxicity of antibodies, particularly in the cancer field, have led to the design of bispecific antibodies: this can occur through various strategies, such as quadroma, thioether-linked Fab' gamma fragments or genetic engineering. Such bispecific antibodies have been developped to enhance immunotherapy, by bridging tumor cells and T cells, or radioimmunotherapy by combining bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells. Multiple further applications can be envisaged such as targeting two different antigens on the same cell, or two epitopes of the same antigen. Although progresses have been slowed by technical constraints, there is little doubt that this class of novel antibodies derivatives will experience a promising development.