Universität zu Köln

Chmielewski, Markus, Hahn, Olga, Rappl, Gunter, Nowak, Michael, Schmidt-Wolf, Ingo H., Hombach, Andreas A. and Abken, Hinrich (2012). T Cells That Target Carcinoembryonic Antigen Eradicate Orthotopic Pancreatic Carcinomas Without Inducing Autoimmune Colitis in Mice. Gastroenterology, 143 (4). S. 1095 - 1110. PHILADELPHIA: W B SAUNDERS CO-ELSEVIER INC. ISSN 0016-5085

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chmielewski, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahn, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED Rappl, Gunter UNSPECIFIED UNSPECIFIED UNSPECIFIED Nowak, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt-Wolf, Ingo H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, Andreas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-481705
DOI:	10.1053/j.gastro.2012.06.037
Journal or Publication Title:	Gastroenterology
Volume:	143
Number:	4
Page Range:	S. 1095 - 1110
Date:	2012
Publisher:	W B SAUNDERS CO-ELSEVIER INC
Place of Publication:	PHILADELPHIA
ISSN:	0016-5085
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLORECTAL-CANCER; THERAPY; IMMUNOTHERAPY; CEA; REGRESSION; RECEPTORS; VACCINES; ANTIBODY Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48170