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Ex vivo expanded NKG2C+ natural killer cells from patient blood for immunotherapy of glioblastoma multiforme

Head and neck tumor research foundation (Stiftung Tumorforschung Kopf-Hals)

For decades there has been no significant improvement in the treatment of patients with primary glioblastoma multiforme (GBM). Since this brain tumor invasively migrates into the normal brain parenchyma, not all tumor cells can be removed neurosurgically. After combined chemo- and radiotherapy but also with the use of novel tumor therapy fields (TTFields), the disease recurs in all cases.

A promising strategy for the treatment of glioblastoma and its recurrence could be an adoptive cellular immunotherapy with NKG2C+ NK cells. By means of the activating NKG2C receptor, these NK cells are able to recognize peptides of the UL40 gene product of various strains of human cytomegalovirus (HCMV), which are presented via HLA-E molecules, and subsequently eliminate virus-infected cells. An increased frequency of NKG2C+ NK cells is therefore found almost exclusively in HCMV-seropositive donors. HCMV-identical peptides have also been identified in glioblastoma tissue and on glioblastoma cells. Especially a peptide from the signal peptide of HLA-G, which is frequently expressed in GBMs, thus represents a promising target structure for an immunotherapy with NKG2C+ NK cells.

On the one hand, our project aims to investigate whether an expansion of NKG2C+ NK cell population from the blood of HCMV-seropositive patients with glioblastoma multiforme is possible. Furthermore, tumor tissue of the patient will be cultured and HLA and KIR gene analyses will be performed in parallel to investigate tolerance or anti-tumor effects of these ex vivo expanded NKG2C+ NK cells after confrontation with autologous glioblastoma cells. Thus, this project is a first step to evaluate the suitability of NKG2C+ NK cells for a future clinical application for the treatment of glioblastoma.

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