Nature biomedical engineering · 2025
Large-scale generation of iNK and CAR-iNK cells from CD34+ haematopoietic stem and progenitor cells for adoptive immunotherapy.
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Hu Fangxiao, Li Jianhuan, Wang Yao, Lin Yunqing, Zhang Jingliao, Xu Jiacheng, Zheng Xiujuan, Weng Qitong, Liu Xiaofei, Geng Yang, Wu Hongling, Liu Lijuan, Peng Huan, Wu Bingyan, Huang Dehao, Xia Chengxiang, Wang Tongjie, Du Xin, Zeng Hui, Dong Fang, Zhang Yingchi, Zhu Xiaofan, Zhang Mengyun, Wang Jinyong
Аннотация
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.