gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

Generation and evaluation of a chimeric NK-cell receptor for an experimental immunotherapy of gliomas

Herstellung und Evaluierung eines chimären NK-Zell-Rezeptors zur experimentellen Immuntherapie von Gliomen

Meeting Abstract

  • corresponding author A. Temme - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, TU Dresden
  • K. Töpfer - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, TU Dresden
  • A. Morgenroth - Institut für Immunologie, Medizinische Fakultät Carl Gustav Carus, TU Dresden
  • E. P. Rieber - Institut für Immunologie, Medizinische Fakultät Carl Gustav Carus, TU Dresden
  • G. Schackert - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, TU Dresden

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 006

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2008/08dgnc274.shtml

Published: May 30, 2008

© 2008 Temme et al.
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Outline

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Objective: Natural killer (NK) cells represent 10-15% of circulating blood leukocytes and belong to the innate immune system. They are indispensable for defeating virus infected or transformed cells. Upon activation NK cells are capable of killing target cells by secretion of granzyme/perforin or the action of death ligands (i.e. TRAIL, Fas-L). The objective of the project was the construction and evaluation of a glioma-specific NK-cell receptor.

Methods: A new immunotherapeutic approach for the treatment of gliomas is the genetic modification of NK cells with chimeric NK-receptors consisting of single chain antibody fragments (scFv) fused to the signal-transducing NK-receptor subunits. As pilot antigen on glioma cells the “Prostate Stem Cell Antigen”, a newly identified glioma associated antigen, was chosen.

An established single antibody fragment against PSCA (scFv-AM1) was fused to DAP12 signal-transducing subunit of the CD94/NKG2C complex and evaluated in vitro.

Results: The scFv-DAP12 construct was efficiently transported to the cell surface in 293T cells and, when integrated in a lentiviral vector, was successfully transduceded in permanent human NK cell lines. Transduced NK cells were capable of destroying PSCA-positive glioma cells whereas PSCA-negative cells were not affected. In other control experiments an appropriate empty vector construct (IgKappa-DAP12-construct) was not able to elicit an NK cell response against PSCA-positive glioma cells and PSCA-negative cells, respectively.

Conclusions: These data support the idea of using modified NK cells for an experimental immunotherapy of gliomas. By further modifying the amount of inhibitory and activating NK-receptor subsets it might be possible to prevail over the glioma cell-mediated inhibitory HLA-E/NKG2A/B-signaling in order to avoid anergy of NK cells.