Antibody drug conjugates: Progress, pitfalls, and promises

Hum Antibodies. 2019;27(1):53-62. doi: 10.3233/HAB-180348.

Abstract

Antibody drug conjugates (ADCs) represent a promising and an efficient strategy for targeted cancer therapy. Comprised of a monoclonal antibody, a cytotoxic drug, and a linker, ADCs offer tumor selectively, reduced toxicity, and improved stability in systemic circulation. Recent approvals of two ADCs have led to a resurgence in ADC research, with more than 60 ADCs under various stages of clinical development. The therapeutic success of future ADCs is dependent on adherence to key requirements of their design and careful selection of the target antigen on cancer cells. Here we review the main components in the design of antibody drug conjugates, improvements made, and lessons learned over two decades of research, as well as the future of third generation ADCs.

Keywords: Monoclonal antibodies; antibody-drug conjugates; cytotoxic drugs; linker; site-specific drug conjugation; target antigens.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents
  • Drug Therapy / trends*
  • Humans
  • Immunoconjugates / therapeutic use*
  • Molecular Targeted Therapy / trends*
  • Neoplasms / immunology*
  • Neoplasms / therapy*

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Immunoconjugates