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Advances in NK cell production

Cellular & Molecular Immunology volume 19, pages 460–481 (2022)Cite this article

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Abstract

Immunotherapy based on natural killer (NK) cells is a promising approach for treating a variety of cancers. Unlike T cells, NK cells recognize target cells via a major histocompatibility complex (MHC)-independent mechanism and, without being sensitized, kill the cells directly. Several strategies for obtaining large quantities of NK cells with high purity and high cytotoxicity have been developed. These strategies include the use of cytokine−antibody fusions, feeder cells or membrane particles to stimulate the proliferation of NK cells and enhance their cytotoxicity. Various materials, including peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs) and NK cell lines, have been used as sources to generate NK cells for immunotherapy. Moreover, genetic modification technologies to improve the proliferation of NK cells have also been developed to enhance the functions of NK cells. Here, we summarize the recent advances in expansion strategies with or without genetic manipulation of NK cells derived from various cellular sources. We also discuss the closed, automated and GMP-controlled large-scale expansion systems used for NK cells and possible future NK cell-based immunotherapy products.

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Acknowledgements

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant no. XDB29030202) and the Ministry of Science and Technology of China (Grant no. 2016YFC1303503).

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  1. These authors contributed equally: Fang Fang, Siqi Xie.

Authors and Affiliations

  1. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China

    Fang Fang, Weihua Xiao & Zhigang Tian

  2. Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China

    Fang Fang, Siqi Xie, Minhua Chen, Yutong Li, Jingjing Yue, Jie Ma, Xun Shu, Yongge He, Weihua Xiao & Zhigang Tian

  3. Institute of Immunology, University of Science and Technology of China, Hefei, 230027, China

    Fang Fang, Siqi Xie, Minhua Chen, Yutong Li, Jingjing Yue, Jie Ma, Xun Shu, Yongge He, Weihua Xiao & Zhigang Tian

  4. Engineering Technology Research Center of Biotechnology Drugs Anhui, University of Science and Technology of China, Hefei, 230027, China

    Fang Fang, Siqi Xie, Minhua Chen, Yutong Li, Jingjing Yue, Jie Ma, Xun Shu, Yongge He, Weihua Xiao & Zhigang Tian

  5. Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei, 230027, China

    Fang Fang, Weihua Xiao & Zhigang Tian

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  1. Fang Fang
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Contributions

FF, SQX, WHX and ZGT conceived and designed the work. FF, SQX, MHC, and YTL wrote the paper. JJY, JM, XS, and YGH reviewed the literature. FF and SQX provided equal contributions to this work.

Corresponding authors

Correspondence to Weihua Xiao or Zhigang Tian.

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The authors declare no competing interests.

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Fang, F., Xie, S., Chen, M. et al. Advances in NK cell production. Cell Mol Immunol 19, 460–481 (2022). https://doi.org/10.1038/s41423-021-00808-3

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  • DOI: https://doi.org/10.1038/s41423-021-00808-3

Keywords

  • NK cells
  • PBMCs
  • UCB
  • iPSCs
  • NK cell lines
  • Genetic manipulation

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