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

Cong-Min Zhang1,2,3, Lin-Yu Yu1,2, Jin-Feng Lv4,5

  • 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.

Personalized Medicine
|May 24, 2018
PubMed
Abstract

Insights

Gene variations impact M701 antibody effectiveness against colorectal cancer (CRC). The CD247 rs2949655 polymorphism is linked to M701

Area of Science:

  • Immunology
  • Oncology
  • Genetics

Background:

  • Colorectal cancer (CRC) is a major global health concern, ranking as the third most common cancer and third leading cause of cancer-related death.
  • M701, a bispecific antibody targeting CD3 and EpCAM, demonstrates significant potential for inducing cytotoxicity against CRC cells.

Purpose of the Study:

  • To determine how specific gene polymorphisms, particularly those related to immune function, influence the efficacy of M701 in targeting CRC cells.
  • To investigate the impact of immuno-related gene variations on M701-mediated cytotoxicity against the HCT116 colorectal cancer cell line.

Main Methods:

  • Peripheral mononuclear blood cells (PMBCs) were collected from 129 healthy volunteers with diverse genotypes.
  • The study analyzed the effects of M701 on the activation and cytotoxic activity of these PMBCs.
  • Genotyping focused on variations within the CD247 gene, specifically the rs2949655 polymorphism.

Main Results:

  • PMBCs from individuals with the CD247 rs2949655 AA genotype exhibited significantly reduced M701-mediated cytotoxicity compared to those with AG/GG genotypes.
  • A notable association was found between the CD247 rs2949655 polymorphism and the level of M701's cytotoxic effect on HCT116 cells.

Conclusions:

  • The CD247 rs2949655 polymorphism is a significant factor influencing M701's efficacy against colorectal cancer.
  • These findings suggest potential for personalized medicine approaches in M701 therapy, tailoring treatment based on patient genetic profiles.
Keywords:
CD3EpCAMbispecific antibodycolorectal cancerimmunotherapypharmacogenomics

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