Author:
Date:
2021-02-05
[Abstract] Activating the STING (stimulator of interferon genes) signaling pathway via administration of STING agonist cyclic GMP-AMP (cGAMP) has shown great promise in cancer immunotherapy. While state-of-the-art approaches have predominantly focused on the encapsulation of cGAMP into liposomes or polymersomes for cellular delivery, we discovered that the recombinant STING protein lacking the transmembrane domain (STINGΔTM) could be used as a functional carrier for cGAMP delivery and elicit type I IFN expression in STING-deficient cell lines. Using this approach, we generated anti-tumoral immunity in mouse melanoma and colon cancer models, providing a potential translatable platform for STING agonist-based immunotherapy. Here, we report the detailed in vitro STING activation ...
[摘要] [摘要]通过给予STING激动剂环状GMP-AMP(cGAMP)激活STING(干扰素基因的刺激物)信号通路已显示出在癌症免疫治疗中的广阔前景。尽管目前最先进的方法主要集中在将cGAMP封装进脂质体或聚合物小体中以进行细胞递送,但我们发现缺少跨膜结构域(STINGΔTM)的重组STING蛋白可以用作cGAMP递送的功能载体。在STING缺陷型细胞系中诱导I型IFN表达。使用这种方法,我们在小鼠黑素瘤和结肠癌模型中产生了抗肿瘤免疫力,为基于STING激动剂的免疫疗法提供了潜在的可翻译平台。在这里,我们报告与cGAMP-STINGΔTM复合物的详细体外STING激活方案,以帮助研究人员进一步开发这种方法。该协议还可以轻松扩展到与STING激活相关的其他应用程序,例如控制各种类型的感染。
[背景]在过去的二十年中,STING(干扰素基因的刺激物)信号传导途径已成为免疫系统的关键特征,并有望成为针对病毒和细菌感染,自身免疫性疾病和癌症的治疗靶标。因此,递送STING激动剂以增强免疫应答已经成为学术机构和制药公司的极大兴趣领域(Ohkuri等人,2017)。尽管现有的努力主要集中在开发合成运载工具上(Shae et ...
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