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The bispecific immunoligand ULBP2‐aCEA redirects natural killer cells to tumor cells and reveals potent anti‐tumor activity against colon carcinoma
Author(s) -
Rothe Achim,
Jachimowicz Ron D.,
Borchmann Sven,
Madlener Marie,
Keßler Jörg,
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,
Strandmann Elke Pogge
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28609
Subject(s) - nkg2d , cancer research , immune system , carcinoembryonic antigen , lymphokine activated killer cell , biology , immunotherapy , immunosurveillance , nk 92 , chimeric antigen receptor , interleukin 21 , immunology , in vitro , t cell , cancer , cytotoxic t cell , biochemistry , genetics
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.