title: T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice.
abstract: OBJECTIVE
  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.
authors: Center for Molecular Medicine Cologne, University of Cologne and Clinic I Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors: Markus
authors: M
authors: Chmielewski
authors: Olga
authors: O
authors: Hahn
authors: Gunter
authors: G
authors: Rappl
authors: Michael
authors: M
authors: Nowak
authors: Ingo H
authors: IH
authors: Schmidt-Wolf
authors: Andreas A
authors: AA
authors: Hombach
authors: Hinrich
authors: H
authors: Abken
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000628:therapy*; D003092:Colitis / Q000276:immunology; D005354:Fibrosarcoma / Q000378:metabolism / Q000628:therapy*; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000637:transplantation*
chemical_list: D002272:Carcinoembryonic Antigen