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73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

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Ex vivo expanded, autologous NKG2C+ natural killer cells from blood of HCMV+ patients for immunotherapy of glioblastoma multiforme

Ex vivo expandierte, autologe NKG2C+ natürliche Killerzellen aus Blut von HCMV+ Patienten zur Immuntherapie des Glioblastoma multiforme

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  • presenting/speaker Susanne Michen - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
  • André Norbert Josef Sagerer - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
  • Willi Jugel - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
  • Alexander Becker - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
  • Monika Füssel - DKMS Life Science Lab GmbH, Dresden, Deutschland
  • Gabriele Schackert - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland; German Cancer Consortium (DKTK), partner site Dresden, Dresden, Deutschland; National Center for Tumor Diseases (NCT/UCC), Dresden, Deutschland; German Cancer Research Center (DKFZ), Heidelberg, Dresden, Deutschland
  • Achim Temme - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland; German Cancer Consortium (DKTK), partner site Dresden, Dresden, Deutschland; National Center for Tumor Diseases (NCT/UCC), Dresden, Deutschland; German Cancer Research Center (DKFZ), Heidelberg, Dresden, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocP048

doi: 10.3205/22dgnc361, urn:nbn:de:0183-22dgnc3618

Published: May 25, 2022

© 2022 Michen et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: This study focuses on NKG2C+ natural killer (NK) cells, a small NK cell subpopulation in the blood of human cytomegalovirus (HCMV) seropositive GBM patients. Beside recognition of peptides derived from classical HLA alleles, these NKG2C+ NK cells are able to recognize a processed HLA-G signal peptide and processed peptides from HCMV-UL40 presented by HLA-E molecules on the surface of glioblastoma cells. Consequently, NKG2C+ NK cells have a higher intrinsic capability to kill specifically glioblastoma cells. In our study we investigated, whether ex vivo expanded NKG2C+ NK cells from HCMV seropositive GBM patients have an anti-tumor effect against autologous and allogenic HLA-E+ glioblastoma cells.

Methods: NK cells were isolated from the blood of HCMV-seropositive GBM patients. NKG2C+ NK cells were specifically expanded for two weeks via a novel feeder cell line modified with an HLA-E trimer presenting the HLA-G-derived VMAPRTLFL peptide. Simultaneously, primary GBM cell cultures were established and tumor tissue was analyzed for GBM-associated immune cell populations by histochemistry and flow cytometry. Subsequently, the cytotoxicity of the ex vivo expanded NKG2C+ NK cells was evaluated by cytotoxicity assays employing autologous and allogeneic primary glioblastoma cells.

Results: Co-culturing isolated primary NK cells with HLA-E+ feeder cells for 14 days resulted in a 128-fold expansion of NKG2C+ NK cells. Interestingly, the GBM tumor tissue of the patients displayed infiltration of NK cells (median 7.5 %; range 0.3 % – 37.1 %), whereas hardly any T lymphocytes were found (median 1.5 %; range 0.7 % – 15.3 %). Initial experiments demonstrated cytotoxicity of expanded NKG2C+ NK cells towards autologous and allogeneic HLA-E+ glioblastoma cells, respectively.

Conclusion: Our results demonstrate a novel highly efficient ex vivo expansion method to gain NKG2C+ NK cells from blood of HCMV seropositive GBM patients. Thus, a first important step was taken to evaluate the suitability of NKG2C+ NK cells for future clinical application for the treatment of GBM.