Effects of immuno-related gene polymorphisms on a bispecific antibody targeting colorectal cancer cell

Per Med. 2018 May 1;15(3):167-179. doi: 10.2217/pme-2017-0071. Epub 2018 May 23.

Abstract

Background: Colorectal cancer (CRC) represents the third most common type of cancer and the third leading cause of death from cancer around the world. M701 is a CD3/EpCAM bispecific antibody that shows promising cytotoxicity toward CRC cells.

Aim: To investigate the influence of immuno-related gene polymorphisms on M701 mediated cytotoxicity to CRC cell HCT116.

Method: We analyzed the influence of the effect of M701 on the activation and cytotoxicity of peripheral mononuclear blood cells from 129 healthy volunteers with different genotypes.

Result: When incubated with M701, peripheral mononuclear blood cells from CD247 rs2949655 AA homozygotes showed significantly lower cytotoxicity than those from AG/GG heterozygotes.

Conclusion: CD247 rs2949655 was significantly associated with the cytotoxicity of M701 to HCT116, which might contribute to personalized medicine of M701.

Keywords: CD3; EpCAM; bispecific antibody; colorectal cancer; immunotherapy; pharmacogenomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific / pharmacology*
  • CD3 Complex / genetics*
  • CD3 Complex / immunology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Epithelial Cell Adhesion Molecule / immunology
  • Genotype
  • HCT116 Cells
  • Healthy Volunteers
  • Humans
  • Pharmacogenomic Variants*
  • Precision Medicine

Substances

  • Antibodies, Bispecific
  • CD3 Complex
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule