Polyspecificity - An emerging trend in the development of clinical antibodies. (March 2023)

• Record Type: Journal Article
• Authors: Sandeep, ; Shinde, Suraj H.; Pande, Abhay H.
• Is Part Of: Molecular immunology. Volume 155(2023)
• Page Start: 175
• Page End: 183
• Publication Date: 2023-03
• Subjects: ADC Antibody-Drug Conjugates -- CAR-T Chimeric Antigen Receptor T-cell -- CAGR Compound annual growth rate -- CDRs Complementary Determining Regions -- CMA Conditional Marketing Authorisation -- HLEP Half-Life Extension Partner -- IBD Inflammatory Bowel Disease -- IL-23 Interleukin-23 -- JNK c-Jun N-terminal Kinase -- MAb Monoclonal Antibody -- NF-κB Nuclear factor kappa B -- PsAb Polyspecific antibody -- PSMA Prostate-Specific Membrane Antigen -- STAT Signal Transducers and Activators of Transcription -- TNF-α Tumor Necrosis Factor-α -- TriKE Trispecific killer cell engager -- VHH Single variable domain on a heavy chain; Pro-inflammatory cytokines -- Inflammatory pathway -- Monoclonal antibody -- Polyspecific antibody -- Cytokine neutralization -- Single domain antibody; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2023.02.005
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract: The essence of the growth and development of therapeutic conventional monoclonal antibodies (MAbs) for the treatment of various disorders is the aptitude of MAbs to precisely bind a target antigen and neutralise or promote its activity. However, the conventional antibodies are monoclonal i.e., both paratopes bind to the same epitope. But most of the pathophysiological conditions are multifaceted, hence targeting/blocking/inhibition of more than one epitope/antigen is more promising than one epitope/antigen. Polyspecific antibodies (PsAbs) have the potential to concurrently bind to more than one target and are the next-generation antibodies that augment efficacy in both clinical and non-clinical contexts. Thus, the trend of engineering and developing various formats of PsAbs is emerging. In this review, we have briefly discussed the importance of antibody polyspecificity and PsAbs approved for clinical use. Subsequently, we have discussed the role of TNF-α and IL-23 in inflammatory diseases and stressed the need for developing anti-TNF-α and anti-IL-23 bispecific antibodies. Highlights: Monoclonal antibodies targeting single epitope/antigen having number of promising clinical and non-clinical applications. Now the trend is changing to polyspecific antibodies targeting more than one epitope/antigen simultaneously. Chronic inflammation claims 3 deaths out of 5 individuals worldwide. TNF-α and IL-23 both are main drivers of chronic inflammation, inhibiting their interactions with their respective receptors using polyspecific antibodies is one of the intriguing treatments to control chronic inflammation. One promising approach to reducing inflammation is the use of PsAb to block TNFα and IL-23 from binding to their receptors.