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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2021

Open Access 01-12-2021 | Cancer Immunotherapy | Review

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

Authors: Ying Gong, Roel G. J. Klein Wolterink, Jianxiang Wang, Gerard M. J. Bos, Wilfred T. V. Germeraad

Published in: Journal of Hematology & Oncology | Issue 1/2021

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Abstract

Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.
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Metadata
Title
Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy
Authors
Ying Gong
Roel G. J. Klein Wolterink
Jianxiang Wang
Gerard M. J. Bos
Wilfred T. V. Germeraad
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2021
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-021-01083-5

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