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Chimeric antigen receptor- and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy

Cellular & Molecular Immunology volume 18, pages 2083–2100 (2021)Cite this article

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Abstract

Chimeric antigen receptor (CAR)-engineered T-cell (CAR-T) therapy has demonstrated impressive therapeutic efficacy against hematological malignancies, but multiple challenges have hindered its application, particularly for the eradication of solid tumors. Innate killer cells (IKCs), particularly NK cells, NKT cells, and γδ T cells, employ specific antigen-independent innate tumor recognition and cytotoxic mechanisms that simultaneously display high antitumor efficacy and prevent tumor escape caused by antigen loss or modulation. IKCs are associated with a low risk of developing GVHD, thus offering new opportunities for allogeneic “off-the-shelf” cellular therapeutic products. The unique innate features, wide tumor recognition range, and potent antitumor functions of IKCs make them potentially excellent candidates for cancer immunotherapy, particularly serving as platforms for CAR development. In this review, we first provide a brief summary of the challenges hampering CAR-T-cell therapy applications and then discuss the latest CAR-NK-cell research, covering the advantages, applications, and clinical translation of CAR- and NK-cell receptor (NKR)-engineered IKCs. Advances in synthetic biology and the development of novel genetic engineering techniques, such as gene-editing and cellular reprogramming, will enable the further optimization of IKC-based anticancer therapies.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81788101) and the CAMS Innovation Fund for Medical Sciences (CIFMS 2019-I2M-5-073).

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Authors and Affiliations

  1. NK CellTech Co., Ltd., Shanghai International Medical Park, Shanghai, China

    Cai Zhang, Yuan Hu, Weihua Xiao & Zhigang Tian

  2. Institute of Immunology, University of Science and Technology of China, Hefei, Anhui, China

    Weihua Xiao & Zhigang Tian

  3. Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Beijing, China

    Zhigang Tian

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ZT and CZ conceptualized this review. CZ wrote the paper. YH and WX engaged in discussion and offered suggestions for the paper. ZT provided guidance on the outline of this review and revised the paper. All authors approved the final submitted version of the paper.

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Correspondence to Cai Zhang or Zhigang Tian.

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Zhang, C., Hu, Y., Xiao, W. et al. Chimeric antigen receptor- and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy. Cell Mol Immunol 18, 2083–2100 (2021). https://doi.org/10.1038/s41423-021-00732-6

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  • DOI: https://doi.org/10.1038/s41423-021-00732-6

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