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

IF 26.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering Pub Date : 2025-10-07 DOI:10.1038/s41551-025-01522-5

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

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引用次数: 0

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.

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从CD34+造血干细胞和祖细胞中大规模生成iNK和CAR-iNK细胞用于过继免疫治疗

嵌合抗原受体（CAR）自然杀伤细胞（CAR- nk）是一种很有前途的替代CAR- t细胞的免疫疗法。在临床试验中，高剂量和多剂量CAR-NK细胞输注对于维持治疗效果至关重要，这需要大规模产生CAR-NK细胞的有效方法。在这里，我们开发了一个三步策略，从人脐带血CD34+造血干细胞和祖细胞（CD34+ HSPCs）中产生高产量的诱导NK （iNK）和CAR-iNK细胞。从单个脐带血单位的CD34+ HSPCs开始，我们的方法产生了1400 - 8300万个成熟的iNK细胞或700 - 3200万个CAR-iNK细胞，这些细胞具有高水平的CD16和CAR表达，并且无法检测到t细胞污染。新鲜的和解冻的iNK细胞和CAR-iNK细胞对各种人类癌细胞都显示出抗肿瘤活性，并延长了人类荷瘤动物的生存时间。CAR- nk细胞的高产量和我们的CAR工程方法降低的成本支持这些细胞在治疗癌症患者中的广泛应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Biomedical Engineering Medicine-Medicine (miscellaneous)

CiteScore

45.30

自引率

1.10%

发文量

138

期刊介绍： Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.