T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice

Gastroenterology. 2012 Oct;143(4):1095-107.e2. doi: 10.1053/j.gastro.2012.06.037. Epub 2012 Jun 27.


Background & aims: New treatment approaches are needed for patients with pancreatic adenocarcinoma. Carcinoembryonic antigen (CEA) is highly expressed on the surface of pancreatic adenocarcinoma cells; we investigated the effects of cytolytic T cells that recognize CEA in a mouse model of pancreatic carcinoma.

Methods: Immune-competent mice that expressed the CEA transgene (CEAtg) in the intestinal and pulmonary tracts were given intrapancreatic injections of Panc02 CEA(+) cells (express CEA and click beetle luciferase) and tumors were grown for 10 days. Mice were then given single intravenous injections of T cells engineered to express a chimeric antigen receptor (CAR) with high specificity, but moderate affinity, for CEA and a luminescence marker.

Results: Injection of the anti-CEA CAR T cells reduced the size of pancreatic tumors to below the limit of detection in all mice and produced long-term tumor eradication in 67% of mice. T cells also eradicated CEA(+) fibrosarcoma cells injected 45 days later. Bioluminescence imaging revealed the accumulation and persistence of the T cells at the tumor site. The efficacy of the T cells did not require lymphodepletion and was not reduced by soluble CEA. Mice developed some noninflammatory infiltrations of CAR(+) T cells in intestine and lung, but there was no evidence of destruction of CEA(+) healthy tissues.

Conclusions: Injection of T cells that target CEA can eradicate tumors grown from CEA(+) pancreatic carcinoma cells in the pancreas of CEAtg mice without autoimmune effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / etiology
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Carcinoembryonic Antigen / immunology*
  • Carcinoembryonic Antigen / metabolism*
  • Carcinoma / metabolism
  • Carcinoma / therapy*
  • Colitis / immunology
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / therapy*
  • Immunotherapy, Adoptive* / adverse effects
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / therapy*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / transplantation*


  • Carcinoembryonic Antigen