Car-engineered nk cells for the treatment of glioblastoma: Turning innate effectors into precision tools for cancer immunotherapy

  • Glioblastoma (GB) is the most common and aggressive primary brain tumor in adults and currently incurable. Despite multimodal treatment regimens, median survival in unselected patient cohorts is <1 year, and recurrence remains almost inevitable. Escape from immune surveillance is thought to contribute to the development and progression of GB. While GB tumors are frequently infiltrated by natural killer (NK) cells, these are actively suppressed by the GB cells and the GB tumor microenvironment. Nevertheless, ex vivo activation with cytokines can restore cytolytic activity of NK cells against GB, indicating that NK cells have potential for adoptive immunotherapy of GB if potent cytotoxicity can be maintained in vivo. NK cells contribute to cancer immune surveillance not only by their direct natural cytotoxicity which is triggered rapidly upon stimulation through germline-encoded cell surface receptors, but also by modulating T-cell mediated antitumor immune responses through maintaining the quality of dendritic cells and enhancing the presentation of tumor antigens. Furthermore, similar to T cells, specific recognition and elimination of cancer cells by NK cells can be markedly enhanced through expression of chimeric antigen receptors (CARs), which provides an opportunity to generate NK-cell therapeutics of defined specificity for cancer immunotherapy. Here, we discuss effects of the GB tumor microenvironment on NK-cell functionality, summarize early treatment attempts with ex vivo activated NK cells, and describe relevant CAR target antigens validated with CAR-T cells. We then outline preclinical approaches that employ CAR-NK cells for GB immunotherapy, and give an overview on the ongoing clinical development of ErbB2 (HER2)-specific CAR-NK cells currently applied in a phase I clinical trial in glioblastoma patients.

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Author:Michael Christian BurgerORCiDGND, Congcong ZhangGND, Patrick Nikolaus HarterORCiDGND, Annette Romanski, Florian Strassheimer, Christian SenftORCiDGND, Torsten Tonn, Joachim Peter SteinbachORCiDGND, Winfried WelsORCiDGND
Pubmed Id:
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Julian Pardo
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/11/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/01/22
Tag:NK-92; adoptive cancer immunotherapy; chimeric antigen receptor; glioblastoma; natural killer cells
Issue:Art. 2683
Page Number:16
First Page:1
Last Page:16
Copyright © 2019 Burger, Zhang, Harter, Romanski, Strassheimer, Senft, Tonn, Steinbach and Wels. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0