Factors influencing the choice of monoclonal antibodies for antibody-drug conjugates

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.

Keywords: Antibody–drug conjugate; Chemotherapy; Drug–antibody ratio; Monoclonal antibodies; Site-specific conjugation; Small-format ADCs.