“NextGen” Biologics: Bispecific Antibodies and Emerging Clinical Results

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEY WORDS:

• Bispecific antibody
• Immunotherapy
• Activated T cells
• Cancer

Article highlights

• Two bispecific antibodies are approved for therapy and >30 are in clinical development; most bispecific antibodies for cancer therapy retarget T cells to kill tumor cells.

• A large number of technology platforms have provided a diverse array of bispecific antibodies with their strengths and limitations.

• Modifications in binding affinities, size, and inclusion of Fc receptors provide desired pharmacodynamic and biological activities.

• The future development of multitarget antigen-binding and immune cell recruiting therapeutic antibodies holds great therapeutic potential.

• Emerging areas of development include dual blockade of different disease pathways, diagnosis, and imaging.

This box summarizes key points contained in the article.

Declaration of interest

A Thakur is a co-founder of Nova Immune Platform Inc. and L Lum co-founded Transtarget Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.