Universität zu Köln

Rothe, Achim, Jachimowicz, Ron D., Borchmann, Sven, Madlener, Marie, Kessler, Joerg, Reiners, Katrin S., Sauer, Maike, Hansen, Hinrich P., Ullrich, Roland T., Chatterjee, Sampurna, Borchmann, Peter, Yazaki, Paul, Koslowsky, Thomas C., Engert, Andreas, Heukamp, Lukas C., Hallek, Michael and von Strandmann, Elke Pogge (2014). The bispecific immunoligand ULBP2-aCEA redirects natural killer cells to tumor cells and reveals potent anti-tumor activity against colon carcinoma. Int. J. Cancer, 134 (12). S. 2829 - 2841. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

NKG2D, an activating receptor expressed on NK cells and T cells, is critically involved in tumor immunosurveillance. In this study, we explored the potential therapeutic utility of the NKG2D ligand ULBP2 for the treatment of colon carcinoma. To this end we designed a fusion protein consisting of human ULBP2 and an antibody-derived single chain targeting the tumor carcinoembryonic antigen (CEA). The bispecific recombinant fusion protein re-directed NK cells towards malignant cells by binding to both, tumor cells and NK cells, and triggered NK cell-mediated target cell killing in vitro. Moreover, tumor growth was significantly delayed in a syngeneic colon carcinoma mouse model in response to immunoligand treatment. The anti-tumor activity could be attributed to the stimulation of immune cells with an elevated expression of the activation marker CD69 on NK, T and NKT cells and the infiltration of CD45+ immune cells into the solid tumor. In summary, it was demonstrated that immunoligands provide specific tumor targeting by NK cells and exert anti-tumor activity in vitro and in vivo. This technology represents a novel immunotherapeutic strategy for solid tumors with the potential to be further developed for clinical applications.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rothe, Achim UNSPECIFIED UNSPECIFIED UNSPECIFIED Jachimowicz, Ron D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Borchmann, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Madlener, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kessler, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiners, Katrin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sauer, Maike UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Hinrich P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullrich, Roland T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chatterjee, Sampurna UNSPECIFIED UNSPECIFIED UNSPECIFIED Borchmann, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Yazaki, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Koslowsky, Thomas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Engert, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED von Strandmann, Elke Pogge UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-435780
DOI:	10.1002/ijc.28609
Journal or Publication Title:	Int. J. Cancer
Volume:	134
Number:	12
Page Range:	S. 2829 - 2841
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NK CELLS; NKG2D RECEPTOR; MEDIATED LYSIS; IN-VITRO; ACTIVATION; EXPRESSION; LIGANDS; CYTOTOXICITY; DIABODY; ANTIGEN Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43578