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GRP78纳米体导向免疫毒素通过STING途径激活先天免疫力,以协同促进瘤免疫疗法

Huifang Wang^1,2, Runhua Zhou³, Chengchao Xu¹

¹Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics, Department of Nuclear Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical CollegeJinan University), Shenzhen, Guangdong, 518020, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|March 26, 2025

概括

一种针对癌细胞的葡萄糖调节蛋白78 (GRP78) 的新疗法显示出有前途. 这种方法增强了抗瘤免疫力,并使瘤对免疫疗法敏感,为癌症治疗提供了新的策略.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

针对性抗原在癌症治疗开发中很少.
葡萄糖调节蛋白78 (GRP78) 的细胞表面表达是潜在的泛癌标.
细胞内膜网膜 (ER) 应激和伴侣转位是恶性瘤的特征.

研究的目的:

开发和评估一种针对GRP78的新型免疫毒素,用于癌症治疗.
为了研究GRP78向免疫毒素的作用机制.
评估这种疗法与现有治疗结合使用的潜力.

主要方法:

使用GRP78特定的C5.5纳米体C5.5开发C5-PE38,一种Pseudomonas外毒素 (PE) 免疫毒素.
在体外评估C5-PE38诱导的ER压力,细胞亡和免疫细胞死亡.
在结直肠癌和黑色素瘤模型中对抗瘤疗效的体内评估.
转录组概况分析免疫微环境调制.
研究STING通路激活及其对免疫细胞透的影响.

主要成果:

C5-PE38对GRP78表现出高度亲和力,并诱导癌细胞死亡.
在临床前模型中观察到抗瘤疗效,毒性最小.
C5-PE38调节瘤免疫微环境,增强先天性和适应性免疫力.
该疗法激活了STING通路,促进了CD8+ T细胞的透.
结合抗PD1疗法在黑色素瘤模型中显示出增强的疗效.

结论:

GRP78纳米体导向疗法 (C5-PE38) 是单一或组合癌症干预的可行策略.
C5-PE38通过STING-依赖机制诱导抗瘤免疫,这是PE38.8的一个新发现.
这种方法为GRP78向性免疫毒素的临床应用提供了宝贵的见解.

关键词:

刺的路径刺的路径细胞表面的葡萄糖调节蛋白78 (GRP78)免疫疗法免疫疗法免疫毒素是一种免疫毒素.有针对性的治疗.

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