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

Created on 08 Oct 2025

Authors

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

Published in

Nature biomedical engineering. Oct 07, 2025. Epub Oct 07, 2025.

Abstract

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 unit of CD34+ HSPCs, our method produces 14-83 million mature iNK cells or 7-32 million CAR-iNK cells with high expression levels of CD16 and CAR and undetectable 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.

PMID:
41057651
Bibliographic data and abstract were imported from PubMed on 08 Oct 2025.

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