Abstract
The advent of chimeric antigen receptor (CAR) T cell therapy has resulted in unprecedented long-term clearance of relapse/refractory hematological malignancies in both pediatric and adult patients. However, severe toxicities, such as cytokine release syndrome and neurotoxicity, associated with CAR T cells affect therapeutic utility; and treatment efficacies for solid tumors are still not impressive. As a result, engineering strategies that modify other immune cell types, especially natural killer (NK) cells have arisen. Owing to both CAR-dependent and CAR-independent (innate immune-mediated) antitumor killing capacity, major histocompatibility complex-independent cytotoxicity, reduced risk of alloreactivity and lack of major CAR T cell toxicities, CAR NK cells constitute one of the promising next-generation CAR immune cells that are also amenable as ‘off-the-shelf’ therapeutics. In this Review, we compare CAR T and CAR NK cell therapies, with particular focus on immunological synapses, engineering strategies and challenges.
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A.D.P. is supported by funding from the V Foundation, Lustgarten Foundation and Veterans Affairs (I01 BX006247).
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Dagher, O.K., Posey, A.D. Forks in the road for CAR T and CAR NK cell cancer therapies. Nat Immunol 24, 1994–2007 (2023). https://doi.org/10.1038/s41590-023-01659-y
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DOI: https://doi.org/10.1038/s41590-023-01659-y
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