The promise of bispecific antibodies

Extract: While monoclonal antibodies closely resemble the naturally occurring immune defense proteins, bispecific antibodies (i.e., antibodies detecting two different antigens) are not found in nature. Both types of antibodies share the feature of antigen specificity that is mediated by the presence of a unique antigen binding site on the antibody. Antigen binding sites exclusively interact with a particular molecular part of an antigen, known as an epitope. Monoclonal IgG (immunoglobulin G) antibodies carry two antigen binding sites for the same epitope, while bispecific antibodies are equipped with two different antigen binding sites with the potential to link two epitopes that could be present on two different cell types. Murine monoclonal antibodies first became available through the hybridoma technology developed by Köhler and Milstein in 1975. Since then they have been improved for therapeutic use by chimerization (only the antigen binding sites remain murine, all other antibody parts are of human origin, e.g., Erbitux), humanization (only the six subregions of the antigen binding site that actually contact the epitope remain murine, e.g., Avastin) or the recovery of fully human antibodies from phage display libraries or from mice transgenic for human immunoglobulin genes (e.g., ABX-EGF, an investigational drug). Several monoclonal antibodies have been approved for human therapy in various disease indications acting either as receptor antagonists, neutralizers of protein receptor ligands or through the recruitment of immune effector functions against pathogenic cells.