Design, synthesis and evaluation of anti-CD38 antibody drug conjugate based on Daratumumab and maytansinoid

Bioorg Med Chem. 2019 Feb 1;27(3):479-482. doi: 10.1016/j.bmc.2018.12.024. Epub 2018 Dec 16.

Abstract

Daratumumab, an FDA approved antibody drug, displays specific targeting ability to abnormal white blood cells overexpressing CD38 and provides efficacious therapy for multiple myeloma. Here, in order to achieve enhanced remission of multiple myeloma, we designed Dara-DM4, antibody drug conjugates (ADCs) by conjugating Daratumumab and DM4 via a disulfide linker. Dara-DM4 showed significantly higher cellular uptake and inhibitory efficacy on MM1S cells that overexpressing CD38 with an IC50 of 0.88 µg/mL post 72 hr treatment. These results support a promising ADCs strategy for multiple myeloma treatment.

Keywords: Antibody drug conjugate; CD38; Maytansinoid; Multiple myeloma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism*
  • Antibodies, Monoclonal / pharmacology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacology*
  • Maytansine / chemistry
  • Maytansine / pharmacology*
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antibodies, Monoclonal
  • Immunoconjugates
  • Maytansine
  • daratumumab