Intracellular trafficking of new anticancer therapeutics: antibody-drug conjugates

Drug Des Devel Ther. 2017 Aug 2:11:2265-2276. doi: 10.2147/DDDT.S135571. eCollection 2017.

Abstract

Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

Keywords: antibody; antibody–drug conjugate; clathrin; endocytosis; intracellular trafficking.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Immunoconjugates / therapeutic use*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Immunoconjugates