MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma

J Cell Biochem. 2019 Apr;120(4):5010-5017. doi: 10.1002/jcb.27776. Epub 2018 Sep 27.

Abstract

Gastric adenocarcinoma is usually diagnosed in late stages, necessitating the use of different therapeutic modalities. Currently, antibody-based therapies have also been approved through with limited clinical efficacy. Reinforcing antibody-based immunotherapy by using chimeric antigen receptor (CAR) T cells may enhance the approach. However, the cells can cause severe on-target and off-tumor toxicities owing to their higher sensitivity to low-level antigen expressions. To address the need for safe and reliable targets, we made a bioinformatics pipeline by which we screened overexpressed genes in the disease for off-tumor sites in many normal tissues. Our inspection showed that MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the probable targets of CAR T cell therapy in gastric adenocarcinoma. The proposed antigenic targets might respond to the need to simultaneously target multiple antigens in a tumor matrix to prevent resistance.

Keywords: antigenic targets; chimeric antigen receptors (CARs); gastric adenocarcinoma; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology*
  • Humans
  • Immunotherapy, Adoptive*
  • Mesothelin
  • Microfilament Proteins / genetics
  • Microfilament Proteins / immunology*
  • Mucin-3 / genetics
  • Mucin-3 / immunology*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*

Substances

  • ANTXR1 protein, human
  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • MSLN protein, human
  • MUC3A protein, human
  • Microfilament Proteins
  • Mucin-3
  • Neoplasm Proteins
  • Receptors, Cell Surface
  • Mesothelin