Research progress and design optimization of CAR-T therapy for pancreatic ductal adenocarcinoma

Cancer Med. 2019 Sep;8(11):5223-5231. doi: 10.1002/cam4.2430. Epub 2019 Jul 3.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Chimeric antigen receptor T cells (CAR-T) are genetically engineered T cells that can specifically kill tumor cells without major histocompatibility complex restriction. Encouraging progress in CAR-T therapy for PDAC has been made in preclinical and early phase clinical trials. Challenges in CAR-T therapy for solid tumors still exist, including immunosuppressive microenvironment, interstitial barrier, poor chemotaxis, and the "on-target, off-tumor" effect. Applying neoantigens of PDAC as targets for CAR-T therapy, recognizing the CAR-T subgroup with better antitumor effect, and designing a CAR-T system targeting stroma of PDAC may contribute to develop a powerful CAR-T therapy for PDAC in the future.

Keywords: CAR-T; PDAC; design optimization; immunotherapy.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / therapy*
  • Chemotaxis / immunology
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism
  • Research
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment / immunology

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen