Prospects for adoptive immunotherapy of pancreatic cancer using chimeric antigen receptor-engineered T-cells

Doraid Alrifai, Debashis Sarker*, John Maher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Adoptive immunotherapy using chimeric antigen receptor (CAR) engineered T-cells is emerging as a powerful new approach to cancer immunotherapy. CARs are fusion molecules that couple the antibody-like binding of a native cell surface target to the delivery of a bespoke T-cell activating signal. Recent studies undertaken by several centers have demonstrated highly compelling efficacy in patients with acute and chronic B-cell malignancies. However, comparable therapeutic activity has not been achieved in solid tumors. Modern management of pancreatic ductal adenocarcinoma (PDAC) remains ineffective, reflected in the virtual equivalence of annual incidence and mortality statistics for this tumor type. Increasing evidence indicates that these tumors are recognized by the immune system, but deploy powerful evasion strategies that limit natural immune surveillance and render efforts at immunotherapy challenging. Here, we review preclinical and clinical studies that have been initiated or completed in an effort to develop CAR-based immunotherapy for PDAC. We also consider the hurdles to the effective clinical development of this exciting new therapeutic modality.

Original languageEnglish
Pages (from-to)50-60
JournalImmunopharmacology and Immunotoxicology
Volume38
Issue number1
Early online date16 Oct 2015
DOIs
Publication statusPublished - Feb 2016

Keywords

  • Chimeric antigen receptor
  • engineered T-cell
  • pancreatic ductal adenocarcinoma
  • tumor-infiltrating lymphocyte

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