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Review
. 2023 Jan 19:13:1081546.
doi: 10.3389/fimmu.2022.1081546. eCollection 2022.

Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Kangdi Yang  1 , Yuze Zhao  2 , Guanqun Sun  3 , Xu Zhang  1 , Jinjin Cao  3 , Mingcong Shao  1 , Xijun Liang  3 , Lina Wang  1
Affiliations
Review

Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Kangdi Yang et al. Front Immunol. .

Abstract

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is an attractive research field in tumor immunotherapy. While CAR is genetically engineered to express certain molecules, it retains the intrinsic ability to recognize tumor cells through its own receptors. Additionally, NK cells do not depend on T cell receptors for cytotoxic killing. CAR-NK cells exhibit some differences to CAR-T cells in terms of more precise killing, numerous cell sources, and increased effectiveness in solid tumors. However, some problems still exist with CAR-NK cell therapy, such as cytotoxicity, low transfection efficiency, and storage issues. Immune checkpoints inhibit immune cells from performing their normal killing function, and the clinical application of immune checkpoint inhibitors for cancer treatment has become a key therapeutic strategy. The application of CAR-T cells and immune checkpoint inhibitors is being evaluated in numerous ongoing basic research and clinical studies. Immune checkpoints may affect the function of CAR-NK cell therapy. In this review, we describe the combination of existing CAR-NK cell technology with immune checkpoint therapy and discuss the research of CAR-NK cell technology and future clinical treatments. We also summarize the progress of clinical trials of CAR-NK cells and immune checkpoint therapy.

Keywords: CAR-NK cell; clinical; immune checkpoint inhibitors; prospect; tumor immunotherapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Development of NK cells in humans.
Figure 2
Figure 2
Distribution of NK cells in humans.
Figure 3
Figure 3
NK cell-mediated killing of tumor cells.
Figure 4
Figure 4
Development and working principle of CAR-NK cells.
Figure 5
Figure 5
Combination of CAR-NK cells and immune checkpoint inhibitors.
See this image and copyright information in PMC

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Grants and funding

The present study was supported by the National Natural Science Foundation of China (No. 82202912, 81774244 and 81303112), the Natural Science Foundation of Shanghai (12ZR1437400), and Shanghai Sailing Project from the Science and Technology Commission of Shanghai Municipality (22YF1458800).

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