Enhancing the efficacy of car t cells in the tumor microenvironment of pancreatic cancer

Janina Henze, Frank Tacke, Olaf Hardt, Frauke Alves, Wa’El Al Rawashdeh

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Pancreatic cancer has the worst prognosis and lowest survival rate among all types of cancers and thus, there exists a strong need for novel therapeutic strategies. Chimeric antigen receptor (CAR)-modified T cells present a new potential option after successful FDA-approval in hematologic malignancies, however, current CAR T cell clinical trials in pancreatic cancer failed to improve survival and were unable to demonstrate any significant response. The physical and environmental barriers created by the distinct tumor microenvironment (TME) as a result of the desmoplastic reaction in pancreatic cancer present major hurdles for CAR T cells as a viable therapeutic option in this tumor entity. Cancer cells and cancer-associated fibroblasts express extracellular matrix molecules, enzymes, and growth factors, which can attenuate CAR T cell infiltration and efficacy. Recent efforts demonstrate a niche shift where targeting the TME along CAR T cell therapy is believed or hoped to provide a substantial clinical added value to improve overall survival. This review summarizes therapeutic approaches targeting the TME and their effect on CAR T cells as well as their outcome in preclinical and clinical trials in pancreatic cancer.

Original languageEnglish
Article number1389
JournalCancers
Volume12
Issue number6
DOIs
StatePublished - Jun 2020
Externally publishedYes

Keywords

  • CAR T cell therapy
  • Cancer-associated fibroblasts
  • Extracellular matrix
  • Immunotherapy
  • Pancreatic cancer
  • Tumor microenvironment

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