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

Drug Discov Today. 2022 Jan;27(1):354-361. doi: 10.1016/j.drudis.2021.09.015. Epub 2021 Sep 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents, Immunological / pharmacology
  • Drug Development* / methods
  • Drug Development* / standards
  • Drug Development* / trends
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunoconjugates / pharmacology*
  • Neoplasms / drug therapy*
  • Quality Improvement

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Immune Checkpoint Inhibitors
  • Immunoconjugates