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. 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.
The use of CAR-NK cell therapies has emerged as a potential alternative to CAR-T cell therapies, due to their ability to overcome therapy-induced side effects. With over 500 CAR-T and 17 CAR-NK cell trials currently underway globally, CAR-immune cell therapies that use precise gene insertion or a dual targeting method with adapter CARs are being investigated. CD19-specific CAR-T cells have shown promise in treating B-cell malignancies, while CAR-NK cells offer an intrinsic tumor killing capacity in addition to their CAR-dependent killing mechanism, potentially impeding tumor immune escape mechanisms.
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. Overcoming the suppressive tumor microenvironment remains an important challenge on the design of CARs before CAR-NK cells, in combination with other therapies, will fulfill their promise.
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Scientific article publishing date: 01/05/2021
Article Identifier: BSC22_424EN