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Review
. 2023 Nov;320(1):217-235.
doi: 10.1111/imr.13255. Epub 2023 Aug 7.

Next-generation chimeric antigen receptors for T- and natural killer-cell therapies against cancer

Ye Li  1 , Katayoun Rezvani  1 , Hind Rafei  1
Affiliations
Review

Next-generation chimeric antigen receptors for T- and natural killer-cell therapies against cancer

Ye Li et al. Immunol Rev. 2023 Nov.

Abstract

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has led to a paradigm shift in the treatment of various hematologic malignancies. However, the broad application of this approach for myeloid malignancies and solid cancers has been limited by the paucity and heterogeneity of target antigen expression, and lack of bona fide tumor-specific antigens that can be targeted without cross-reactivity against normal tissues. This may lead to unwanted on-target off-tumor toxicities that could undermine the desired antitumor effect. Recent advances in synthetic biology and genetic engineering have enabled reprogramming of immune effector cells to enhance their selectivity toward tumors, thus mitigating on-target off-tumor adverse effects. In this review, we outline the current strategies being explored to improve CAR selectivity toward tumor cells with a focus on natural killer (NK) cells, and the progress made in translating these strategies to the clinic.

Keywords: T cells; antitumor immunotherapy; chimeric antigen receptor (CAR); natural killer (NK) cells; synthetic immune cell engineering.

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Conflict of interest statement

COMPETING INTERESTS

Y.L., H.R., K.R. and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Takeda Pharmaceutical and Affimed GmbH. K.R. participates on the Scientific Advisory Board for GemoAb, AvengeBio, Virogin Biotech, GSK, Bayer, Navan Technologies, and Caribou Biosciences. K.R. is the scientific founder of Syena. The remaining authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Strategies to explore novel antigen-targeting domains.
Figure 2.
Figure 2.
Strategies to advance CAR NK cell mediated on-target anti-tumor activity.
Figure 3.
Figure 3.
Strategies to overcome CAR NK cell-mediated on-target off-tumor toxicity.
See this image and copyright information in PMC

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