Factors influencing the choice of monoclonal antibodies for antibody–drug conjugates. Issue 1 (January 2022)

• Record Type: Journal Article
• Authors: Hasan, Md. Mahbub; Laws, Mark; Jin, Peiqin; Rahman, Khondaker Miraz
• Is Part Of: Drug discovery today. Volume 27:Issue 1(2022)
• Page Start: 354
• Page End: 361
• Publication Date: 2022-01
• Subjects: Monoclonal antibodies -- Antibody–drug conjugate -- Chemotherapy -- Small-format ADCs -- Site-specific conjugation -- Drug–antibody ratio; Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2021.09.015
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: Genetically engineered mAbs allow consistent DAR via site-specific conjugation. Microbial transglutaminase can be utilized for site-specific conjugation reactions. Non-internalizing mAbs are showing promise for targeting solid tumours. Fc region-mediated immune functions can facilitate desired therapeutic outcomes. Small-format ADCs can demonstrate similar cytotoxicity to conventional ADCs. Abstract: In antibody–drug conjugates (ADCs), monoclonal antibodies (mAbs) act as carriers for a cytotoxic payload providing the therapy with targeted action against cells expressing a target cell surface antigen. An appropriate choice of mAb is crucial to developing a successful ADC for clinical development. However, problems such as immunogenicity, poor pharmacokinetic (PK) and pharmacodynamic (PD) profiles and variable drug–antibody ratios (DARs) plague ADCs. In this review, we detail recent mAb-based innovations and factors that should be considered to overcome these problems to achieve a new generation of more effective ADC therapeutics.