CEACAM7 Is an Effective Target for CAR T-cell Therapy of Pancreatic Ductal Adenocarcinoma

Clin Cancer Res. 2021 Mar 1;27(5):1538-1552. doi: 10.1158/1078-0432.CCR-19-2163. Epub 2021 Jan 21.

Abstract

Purpose: To investigate whether CEACAM7 represents a novel therapeutic target for treating pancreatic ductal adenocarcinoma (PDAC) and to generate CEACAM7-targeting CAR T cells to test this hypothesis.

Experimental design: We identified CEACAM7 (CGM2), a member of the CEA family of proteins with expression restricted to the colon and pancreas, as a potential CAR T-cell target for PDAC. We probed a panel of PDAC tumor sections as well as patient-derived PDAC cell cultures for CEACAM7 expression. We generated CAR-targeting CEACAM7, and assessed antitumor efficacy of CEACAM7 CAR T cells using in vitro and in vivo models.

Results: We show here that CEACAM7 is expressed in a large subset of PDAC tumors, with low to undetectable expression in all normal tissues tested. CEACAM7 is also expressed in primary PDAC cultures isolated from patient-derived tumors, with high expression within the cancer stem cell-enriched subset. CAR T cells targeting CEACAM7 are capable of targeting antigen-expressing tumor cells, and mediate remission in patient-derived xenograft tumors.

Conclusions: We identify CEACAM7 as a potential therapeutic target in PDAC and describe the development of CEACAM7-targeted CAR T cells with efficacy against PDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Apoptosis
  • Carcinoembryonic Antigen
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy*
  • Cell Proliferation
  • GPI-Linked Proteins / antagonists & inhibitors
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Prognosis
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Neoplasm
  • CEACAM7 protein, human
  • Carcinoembryonic Antigen
  • GPI-Linked Proteins

Supplementary concepts

  • Pancreatic Carcinoma