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

Full text not available from this repository.

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:
CreatorsEmailORCIDORCID Put Code
Chmielewski, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahn, OlgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rappl, GunterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nowak, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt-Wolf, Ingo H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hombach, Andreas A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abken, HinrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
COLORECTAL-CANCER; THERAPY; IMMUNOTHERAPY; CEA; REGRESSION; RECEPTORS; VACCINES; ANTIBODYMultiple languages
Gastroenterology & HepatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48170

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item