Intracellular Catabolism of an Antibody Drug Conjugate with a Noncleavable Linker

Drug Metab Dispos. 2015 Sep;43(9):1341-4. doi: 10.1124/dmd.115.064253. Epub 2015 Jun 22.

Abstract

Antibody drug conjugates are emerging as a powerful class of antitumor agents with efficacy across a range of cancers; therefore, understanding the disposition of this class of therapeutic is crucial. Reported here is a method of enriching a specific organelle (lysosome) to understand the catabolism of an anti-CD70 Ab-MCC-DM1, an antibody drug conjugate with a noncleavable linker. With such techniques a higher degree of concentration-activity relationship can be established for in vitro cell lines; this can aid in understanding the resultant catabolite concentrations necessary to exert activity.

MeSH terms

  • CD27 Ligand / immunology
  • Cell Line, Tumor
  • Humans
  • Immunoconjugates / metabolism*
  • Lysosomes / metabolism*
  • Pharmaceutical Preparations / metabolism*

Substances

  • CD27 Ligand
  • Immunoconjugates
  • Pharmaceutical Preparations