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<p>Chimaeric antigen receptor (CAR) natural killer (CAR-NK) cells are a promising alternative to CAR-T cells for immunotherapies. High and multiple doses of CAR-NK cell infusions are essential to maintain therapeutic efficacy in clinical trials, requiring efficient methods for generating CAR-NK cells at scale. Here we develop a three-step strategy to generate high yields of induced NK (iNK) and CAR-iNK cells from human umbilical cord blood CD34<sup>+</sup> haematopoietic stem and progenitor cells (CD34<sup>+</sup> HSPCs). Starting from a single umbilical cord blood CD34<sup>+</sup> HSPC, our reliable method efficiently produces 14–83 million mature iNK cells or 7–32 million CAR-iNK cells with high expression levels of CD16 and zero T-cell contamination. Both fresh and thawed iNK and CAR-iNK cells demonstrate anti-tumour activities against various human cancer cells and prolong the survival of human tumour-bearing animals. The high yields of CAR-NK cells and reduced costs of our method’s CAR engineering support the broad applications of these cells for treating cancer patients.</p>

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Large-scale generation of iNK and CAR-iNK cells from CD34+ haematopoietic stem and progenitor cells for adoptive immunotherapy

  • 期刊论文

  • 发表日期：

    2025年10月7日

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  • Fangxiao Hu,
  • Jianhuan Li,
  • Yao Wang,
  • Yunqing Lin,
  • Jingliao Zhang,
  • Jiacheng Xu,
  • Xiujuan Zheng,
  • Qitong Weng,
  • Xiaofei Liu,
  • Yang Geng,
  • Hongling Wu,
  • Lijuan Liu,
  • Huan Peng,
  • Bingyan Wu,
  • Dehao Huang,
  • Chengxiang Xia,
  • Tongjie Wang,
  • Xin Du,
  • Hui Zeng,
  • Fang Dong,
  • Yingchi Zhang,
  • Xiaofan Zhu,
  • Mengyun Zhang,
  • Jinyong Wang

摘要

Chimaeric antigen receptor (CAR) natural killer (CAR-NK) cells are a promising alternative to CAR-T cells for immunotherapies. High and multiple doses of CAR-NK cell infusions are essential to maintain therapeutic efficacy in clinical trials, requiring efficient methods for generating CAR-NK cells at scale. Here we develop a three-step strategy to generate high yields of induced NK (iNK) and CAR-iNK cells from human umbilical cord blood CD34+ haematopoietic stem and progenitor cells (CD34+ HSPCs). Starting from a single umbilical cord blood CD34+ HSPC, our reliable method efficiently produces 14–83 million mature iNK cells or 7–32 million CAR-iNK cells with high expression levels of CD16 and zero T-cell contamination. Both fresh and thawed iNK and CAR-iNK cells demonstrate anti-tumour activities against various human cancer cells and prolong the survival of human tumour-bearing animals. The high yields of CAR-NK cells and reduced costs of our method’s CAR engineering support the broad applications of these cells for treating cancer patients.