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工程化 iPSC 来源 NK 细胞:转化型固有抗癌免疫治疗的最新创新

英文原题:Engineered iPSC-derived natural killer cells: recent innovations in translational innate anti-cancer immunotherapy.

查看英文原题

Engineered iPSC-derived natural killer cells: recent innovations in translational innate anti-cancer immunotherapy.

PubMed 2025/07/10(内容时间) Clin Transl Immunology Q3 · IF 3.4(JCR 2025)

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中文摘要

自然杀伤(NK)细胞日益被认为是一种强效的杀肿瘤细胞,可用于癌症免疫治疗。它们对肿瘤细胞的先天细胞毒性,以及在患者中引起移植或毒性问题的风险较低,使其成为同种异体过继细胞免疫治疗中值得探索的有价值选择。然而,从外周血中获取NK细胞在可扩展性、一致性和变异性方面存在挑战。诱导多能干细胞(iPSC)正逐渐成为一个平台,可通过高度可控的流程制造特定细胞,为细胞治疗提供共同的细胞来源,并有望成为可进行基因修饰的NK细胞的取之不尽的来源。本综述重点介绍了在明确培养体系中生成iPSC来源NK细胞领域的最新进展,以及通过基因修饰改进iPSC-NK细胞治疗的进展。我们进一步讨论了iPSC库的建设,并探讨了这些细胞在下一代免疫治疗中的潜力。最后,我们总结了通过对iPSC进行基因修饰所实现的iPSC来源NK(iNK)细胞在体外和体内靶向肿瘤、扩增、持久性和细胞毒性功能方面的改进,以及近期相关临床试验。

展开英文摘要原文

Natural killer (NK) cells are increasingly recognised as potent tumoricidal agents that can be utilised for cancer immunotherapy. Their innate cytotoxicity against tumor cells, and reduced risk of causing transplantation or toxicity issues in patients, makes them a valuable option for exploration in allogeneic adoptive cell immunotherapies.

However, sourcing NK cells from peripheral blood poses challenges in terms of scalability, consistency and variability. Induced pluripotent stem cells (iPSCs) are emerging as a platform to create specific cells with highly controlled processes, allowing for a common cell source for cell therapies and offering a promising inexhaustible source of genetically modifiable NK cells.

This review highlights recent developments in the field of generating iPSC-derived NK cells in defined culture systems, and advancements in genetic modification to improve iPSC-NK cell therapy.

We further discuss the development of iPSC banks and examine the potential of these cells in next-generation immunotherapies.

Finally, we summarise the improvements in cancer targeting, expansion, persistence and cytotoxic functionality of iPSC-derived NK (iNK) cells both in vitro and in vivo , achieved through genetic modification of iPSCs, as well as recent related clinical trials.

论文信息

作者
Sun J、Elliott M、Souza-Fonseca-Guimaraes F
单位
Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences The University of Queensland Brisbane QLD Australia.Australia
文献类型
综述
期刊
Clinical & translational immunology2025
原文标识
PubMed 40655896 · DOI 10.1002/cti2.70045