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:
CreatorsEmailORCIDORCID Put Code
Rothe, AchimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jachimowicz, Ron D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borchmann, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madlener, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kessler, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiners, Katrin S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sauer, MaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, Hinrich P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ullrich, Roland T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chatterjee, SampurnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borchmann, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yazaki, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koslowsky, Thomas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engert, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heukamp, Lukas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Strandmann, Elke PoggeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
NK CELLS; NKG2D RECEPTOR; MEDIATED LYSIS; IN-VITRO; ACTIVATION; EXPRESSION; LIGANDS; CYTOTOXICITY; DIABODY; ANTIGENMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43578

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