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瘤微环境响应纳米囊输送CRISPR/Cas9来重编程肝瘤癌瘤中的免疫抑制微环境

Lei He¹, Zhaozhao Li¹, Danjie Su²

¹State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|May 5, 2024

概括

在肝细胞癌 (HCC) 中,基因编辑以去除生长分化因子15 (GDF15) 逆转免疫抑制. 这种方法通过重新编程瘤微环境来提高癌症免疫治疗的有效性.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
基因治疗基因治疗
纳米技术纳米技术

背景情况:

肝细胞癌 (HCC) 免疫疗法疗效有限,需要新的治疗点.
增长分化因子15 (GDF15) 在HCC上调,与预后不佳相关,并促进瘤免疫抑制.
通过基因编辑准GDF15提供了一个潜在的策略来逆转免疫抑制瘤微环境.

研究的目的:

调查CRISPR/Cas9基因编辑的潜力,以在HCC中淘汰GDF15.
开发一种针对CRISPR/Cas9向HCC细胞的向传递系统.
评估GDF15淘汰对HCC免疫微环境和免疫治疗反应的影响.

主要方法:

生物信息学分析确定GDF15是HCC的一个关键目标.
开发具有二硫化键 (SNC_SS) 的SP94结合纳米囊 (SNC),用于有针对性的CRISPR/Cas9传递.
在体内研究中使用SNC_SS传递CRISPR/Cas9用于HCC模型中的GDF15淘汰.
CyTOF分析用于评估瘤免疫微环境的变化.

主要成果:

SNC_SS有效地准了HCC细胞,并提供了CRISPR/Cas9系统.
GDF15淘汰赛显著抑制了HCC的进展,并促进了免疫治疗.
赛托夫 (CyTOF) 分析显示,瘤转向更具免疫性的瘤微环境,杀伤性免疫细胞增加,抑制性免疫细胞减少.

结论:

有针对性的CRISPR/Cas9介导的GDF15淘汰是HCC治疗的一个有前途的策略.
这种方法可以重新编程瘤免疫微环境,提高免疫治疗的疗效.
具有SP94功能的,对GSH敏感的纳米囊为HCC的基因编辑提供了有效的输送系统.

关键词:

这就是CRISPR/Cas9的作用.在GDF15中,GDF15是GDF15中的一个.肝细胞癌是肝细胞癌.免疫微观环境免疫微环境这是一个纳米囊纳米囊.

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