"NextGen" Biologics: Bispecific Antibodies and Emerging Clinical Results

Bispecific antibodies (BsAb) are emerging as a novel approach for dual targeting strategies. Two bispecific antibodies are approved for therapy and >30 are in clinical development. The first generation of BsAb were produced by chemical cross-linking or hybridoma technology; with the recent advent of genetic and protein engineering technologies numerous formats of bispecific antibodies have emerged using either the fragments of IgG or whole IgG molecules. Further areas of development include dual blockade of different disease pathways, diagnosis and imaging.

Biologics, including bi- or multi-specific antibodies and T cell-based approaches are rapidly changing the landscape of cancer therapeutics. New engineering platforms for bi- or multi-specific antibodies and scaffolds offer improved efficacy and reduced toxicities over IgG-based monoclonal antibodies. Preclinical and clinical studies using different formats of BsAbs are described in this review using PubMed as a literature search tool.

A comprehensive presentation of preclinical data and clinical trials evaluating the various formats of BsAbs indicate their safety and efficacy. However, a vast opportunity to fine tune physical properties and functional activity of biologics to improve the stability, engagement of cytotoxic CD8 T cells and multi-antigen targeting strategy through protein engineering holds a greater therapeutic potential.