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International Journal of Hematology
Published in: International Journal of Hematology 5/2021

01-11-2021 | Solid Tumor | Progress in Hematology

Engineering the next generation of CAR-NK immunotherapies

Authors: Alexander Biederstädt, Katayoun Rezvani

Published in: International Journal of Hematology | Issue 5/2021

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Abstract

Over the past few years, cellular immunotherapy has emerged as a novel treatment option for certain forms of hematologic malignancies with multiple CAR-T therapies now routinely administered in the clinic. The limitations of generating an autologous cell product and the challenges of toxicity with CAR-T cells underscore the need to develop novel cell therapy products that are universal, safe, and potent. Natural killer (NK) cells are part of the innate immune system with unique advantages, including the potential for off-the-shelf therapy. A recent first-in-human trial of CD19-CAR-NK infusion in patients with relapsed/refractory lymphoid malignancies proved safe with promising clinical activity. Building on these encouraging clinical responses, research is now actively exploring ways to further enhance CAR-NK cell potency by prolonging in vivo persistence and overcoming mechanisms of functional exhaustion. Besides these strategies to modulate CAR-NK cell intrinsic properties, there are increasing efforts to translate the successes seen in hematologic malignancies to the solid tumor space. This review will provide an overview on current trends and evolving concepts to genetically engineer the next generation of CAR-NK therapies. Emphasis will be placed on innovative multiplexed engineering approaches including CRISPR/Cas9 to overcome CAR-NK functional exhaustion and reprogram immune cell metabolism for enhanced potency.
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Metadata
Title
Engineering the next generation of CAR-NK immunotherapies
Authors
Alexander Biederstädt
Katayoun Rezvani
Publication date
01-11-2021
Publisher
Springer Singapore
Keyword
Solid Tumor
Published in
International Journal of Hematology / Issue 5/2021
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-021-03209-4

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