NK cells armed with chimeric antigen receptors (CAR): roadblocks to successful development

Bashiri Dezfouli, A., Yazdi, M., Pockley, A.G. ORCID: 0000-0001-9593-6431, Khosravi, M., Kobold, S., Wagner, E. and Multhoff, G., 2021. NK cells armed with chimeric antigen receptors (CAR): roadblocks to successful development. Cells, 10 (12): 3390.

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Abstract

In recent years, cell-based immunotherapies have demonstrated promising results in the treatment of cancer. Chimeric antigen receptors (CARs) arm effector cells with a weapon for targeting tumor antigens, licensing engineered cells to recognize and kill cancer cells. The quality of the CAR-antigen interaction strongly depends on the selected tumor antigen and its expression density on cancer cells. CD19 CAR-engineered T cells approved by the Food and Drug Administration have been most frequently applied in the treatment of hematological malignancies. Clinical challenges in their application primarily include cytokine release syndrome, neurological symptoms, severe inflammatory responses, and/or other off-target effects most likely mediated by cytotoxic T cells. As a consequence, there remains a significant medical need for more potent technology platforms leveraging cell-based approaches with enhanced safety profiles. A promising population that has been advanced is the natural killer (NK) cell, which can also be engineered with CARs. NK cells which belong to the innate arm of the immune system recognize and kill virally infected cells as well as (stressed) cancer cells in a major histocompatibility complex I independent manner. NK cells play an important role in the host’s immune defense against cancer due to their specialized lytic mechanisms which include death receptor (i.e., Fas)/death receptor ligand (i.e., Fas ligand) and granzyme B/perforin-mediated apoptosis, and antibody-dependent cellular cytotoxicity, as well as their immunoregulatory potential via cytokine/chemokine release. To develop and implement a highly effective CAR NK cell-based therapy with low side effects, the following three principles which are specifically addressed in this review have to be considered: unique target selection, well-designed CAR, and optimized gene delivery.

Item Type: Journal article
Publication Title: Cells
Creators: Bashiri Dezfouli, A., Yazdi, M., Pockley, A.G., Khosravi, M., Kobold, S., Wagner, E. and Multhoff, G.
Publisher: MDPI AG
Date: 1 December 2021
Volume: 10
Number: 12
Identifiers:
NumberType
10.3390/cells10123390DOI
1502430Other
Rights: Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 15 Dec 2021 11:54
Last Modified: 15 Dec 2021 11:54
URI: http://irep.ntu.ac.uk/id/eprint/45129

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