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多能干细胞衍生的仿真抗原受体-自然杀手细胞,准表皮生长因子受体2用于癌症免疫治疗

Jongsuk Han¹, Chaeyeon Jin¹, Sae-Byeok Hwang²

¹Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea.

|October 31, 2025

概括

针对HER2的多能干细胞衍生的仿真抗原受体天然杀手 (CAR-NK) 细胞显示增强了癌细胞的杀死. 这种可再生的CAR-NK细胞平台提供了一种可扩展的方法,用于对HER2阳性瘤的全源免疫疗法.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
生物技术是生物技术.

背景情况:

化学抗原受体自然杀手 (CAR-NK) 细胞是一种有前途的全基性免疫疗法.
多能干细胞 (PSC) 为NK细胞提供了可再生的来源,克服了初级NK细胞的局限性.
人类表皮生长因子受体2 (HER2) 是许多固体瘤中过度表达的点.

研究的目的:

开发和评估针对HER2进行癌症免疫治疗的PSC衍生的CAR-NK细胞.
评估产生可扩展和可再生的CAR-NK细胞产品的可行性.

主要方法:

设计了一个与GFP相关的反HER2 CAR结构.
通过lentiviral转导引入CAR结构到PSC中,建立稳定的克隆.
在无外基因,无料条件下将分化的PSC转化为NK细胞.
评估了PSC衍生的CAR-NK细胞的CAR表达,表型和细胞毒性.

主要成果:

产生了稳定的PSC克隆,共同表达抗HER2的CAR和GFP.
在NK细胞分化后,CAR表达在NK细胞中保持.
来自PSC的CAR-NK细胞表现出与野生类型的PSC-NK细胞相似的表型和功能.
观察到对HER2阳性癌细胞系的增强细胞毒性.

结论:

来自PSC的抗HER2 CAR-NK细胞代表了一个强大而可扩展的免疫疗法平台.
这种方法可以扩展到针对各种瘤相关抗原.
进一步的开发有可能为有效的全基细胞基癌症疗法提供潜力.

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