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Updated: Aug 12, 2026

Generation of Knock-out Primary and Expanded Human NK Cells Using Cas9 Ribonucleoproteins

Generation of Knock-out Primary and Expanded Human NK Cells Using Cas9 Ribonucleoproteins

Published on: June 14, 2018

来自多能干细胞的工程 CRO-CD7 CAR-NK 细胞避免兄弟杀戮,有效地抑制人类T细胞恶性瘤

Yunqing Lin^1,2, Ziyun Xiao^1,2, Fangxiao Hu³

¹State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

Journal of hematology & oncology

|May 19, 2025

概括

这项研究对来自人类多能干细胞 (hPSC) 的CAR-NK细胞进行了工程设计,以克服T细胞恶性瘤治疗中的兄弟杀戮. 由此产生的CAR-NK细胞表现出强大的抗瘤活性,并改善了体内持续性,提供了一个有前途的新疗法.

科学领域:

免疫治疗是一种免疫疗法.
干细胞生物学干细胞生物学
血液瘤学血液瘤学

背景情况:

T细胞恶性瘤是具有有限治疗选择的侵袭性癌症.
CAR-NK细胞疗法显示出前景,但面临诸如细胞兄弟杀戮和制造困难等挑战.
癌细胞和正常NK细胞上的CD7表达导致兄弟杀伤,限制了治疗的有效性.

研究的目的:

开发一种抗兄弟杀伤的CAR-NK细胞疗法,用于T细胞恶性瘤.
为了将CARs设计成人类多能干细胞 (hPSCs),以进行可扩展的NK细胞生产.
在体内增强CAR-NK细胞定位和持久性.

主要方法:

通过淘汰CD7并引入CD7 CAR,基因改造的hPSCs.
分化改造的hPSCs变成CD7淘汰CD7CAR诱导的NK (iNK) 细胞.
在iNK细胞中过度表达CXCR4,产生CRO-CD7CAR-iNK细胞,用于体内追踪和T-ALL异种移植模型中的疗效评估.

主要成果:

CD7 KO-CD7 CAR-iNK 细胞避免了兄弟杀伤,并对 CD7+ T 细胞瘤表现出强有力的特异性抗瘤活性.
过度表达CXCR4增强了CRO-CD7 CAR-iNK细胞归本和体内持久性.
在T-ALL小鼠模型中,CRO-CD7 CAR-iNK细胞显著抑制了瘤生长,并延长了生存时间.

结论:

开发了一种可靠的策略,用于从hPSC中大规模生成抗兄弟杀伤的CD7 CAR-iNK细胞.
这些工程iNK细胞表现出强大的抗瘤作用.
这种方法为治疗T细胞恶性瘤提供了一个有前途的细胞产品.

关键词:

CD7 CAR-NK-NK 它们的基因.在CXCR4中,CXCR4是最常见的.抵制杀害兄弟的行为人类多能干细胞是人类多能干细胞.坚持不坚持不所有的T-ALL.

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