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纳米颗粒介导的内基因编辑针对PD-L1和Galectin-9,以改善癌症免疫治疗

Tianxu Fang¹, Yueyang Deng¹, Mo Chen¹

¹Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.

|June 26, 2025

概括

这项研究开发了使用纳米粒子输送的CRISPR-Cas9.9在瘤细胞中的PD-L1和Galectin-9的双重淘汰策略. 这种方法可以增强抗瘤免疫力,并显著抑制瘤生长和转移.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

瘤细胞表达PD-L1和Galectin-9 (Gal-9),这些细胞通过T细胞中介杀死TIM3/Gal-9通路来抑制.
目前的免疫检查点抑制剂具有局限性,包括低反应率和全身毒性.

研究的目的:

开发一种双淘汰方法,针对瘤细胞中的PD-L1和Gal-9,以改善癌症免疫疗法.
为CRISPR-Cas9/sgRNA核糖蛋白 (RNP) 联合递送和抗瘤免疫启动而设计酸纳米粒子 (CaP NPs).

主要方法:

设计的CaPNP用于共同传递CRISPR-Cas9/sgRNARNARNANPs.
给RNP加载的CaPNP进行内注射,以实现PD-L1和Gal-9的双重淘汰.
研究了Ca2+过载和DAMPs释放在增强免疫反应中的作用.

主要成果:

在瘤细胞中实现了PD-L1和Gal-9的有效淘汰,引起了强大的抗瘤免疫力.
CaP NP 降解释放 DAMP,进一步促进 T 细胞介导的抗瘤反应.
在小鼠模型中显著抑制了初级和远程瘤生长.
由于循环瘤细胞的双重淘汰,观察到肺转移的减少.

结论:

通过纳米粒子辅助的CRISPR-Cas9对PD-L1和Gal-9进行双重淘汰,是癌症免疫疗法的有希望的策略.
这种方法有效地触发了局部和全身的抗瘤免疫力,导致瘤生长的抑制和转移的减少.

关键词:

克里斯普尔-Cas9是什么意思酸纳米颗粒酸纳米颗粒循环中的瘤细胞.盖莱克-9的使用方法基因编辑基因编辑免疫检查站封锁免疫检查站封锁在PD-L1中.

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