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用SL^dacA增强瘤特异性免疫力:一种弱的沙门氏菌介导的c-di-AMP输送系统,针对STING通路

Yuanjia Huang¹, Linghua Piao², Xiande Liu¹

¹School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation center of One Health, Hainan University, No. 58 Renmin Avenue, Haikou 570228, China.

International journal of pharmaceutics

|September 27, 2024

概括

工程细菌为瘤提供STING激动剂,增强T细胞反应. 这种方法可以提高抗瘤免疫力,同时最大限度地减少副作用,为癌症免疫治疗提供了一个有前途的新策略.

科学领域:

免疫学免疫学免疫学
微生物学微生物学
在瘤学瘤学.

背景情况:

刺痛激动剂激活抗瘤T细胞反应,但缺乏瘤特异性,冒着不良影响的风险.
减弱型沙门氏菌 typhimurium △ppGpp (S.t△ppGpp) 提供高瘤特异性和抗瘤免疫性.
携带STING激动剂的沙门氏菌的治疗潜力在很大程度上尚未被探索.

研究的目的:

为了设计一种沙门氏菌株 (SLdacA),以有针对性地提供STING激动剂.
为了评估由工程细菌诱导的抗瘤免疫反应.
研究STING/I型干扰素途径在细菌介导免疫治疗中的作用.

主要方法:

改造了S.t△ppGpp以产生c-di-AMP (一种STING激动剂),产生了SLdacA菌株.
评估了树突细胞的成熟和M1巨细胞的极化.
在瘤微环境中测量了I型干扰素的产生和T细胞的激活.

主要成果:

SLdacA增强了树突细胞的成熟和M1巨细胞的极化.
工程细菌诱导了I型干扰素的产生,招募和激活效应T细胞.
STING/I型干扰素途径调解了抗瘤免疫反应.

结论:

SLdacA有效地提供STING激动剂,刺激强大的抗瘤免疫反应.
通过细菌介导的STING激动剂的输送显示出对协同性癌症免疫治疗的希望.
与传统的STING激动剂相比,有针对性的输送提高了安全性和有效性.

关键词:

减弱型沙门氏菌 typhimurium 是一种树突细胞成熟的过程刺痛激动剂刺痛激动剂激活T细胞的激活过程 c-di-AMP 这是一个很好的方法.

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