Antibody drug conjugates of cleavable amino-benzoyl-maytansinoids

Bioorg Med Chem. 2020 Dec 1;28(23):115785. doi: 10.1016/j.bmc.2020.115785. Epub 2020 Oct 11.

Abstract

ADCs based on the natural product maytansine have been successfully employed clinically. In a previous report, ADCs based on hydrophilic non-cell permeable maytansinoids was presented. The authors in this report further explore the maytansine scaffold to develop tubulin inhibitors capable of cell permeation. The research resulted in amino-benzoyl-maytansinoid payloads that were further elaborated with linkers for conjugating to antibodies. This approach was applied to MUC16 tumor targeting antibodies for ovarian cancers. A positive control ADC was evaluated alongside the amino-benzoyl-maytansinoid ADC and the efficacy observed was equivalent while the isotype control ADCs had no effect.

Keywords: Antibody; Antibody drug conjugate; MUC16; Maytansinoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / metabolism*
  • Immunoconjugates / pharmacology
  • Immunoconjugates / therapeutic use
  • Maytansine / chemistry*
  • Maytansine / metabolism
  • Mice, SCID
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Structure-Activity Relationship
  • Transplantation, Heterologous
  • Tubulin Modulators / chemistry*
  • Tubulin Modulators / metabolism

Substances

  • Immunoconjugates
  • Tubulin Modulators
  • Maytansine