STING激动剂细胞筛选模型的建立和应用

Establishment and application of STING agonist in-vitro screening model

肿瘤免疫疗法已成为当今抗癌药物研发的重要领域, STING激动剂的研究为肿瘤免疫治疗提供了新思路。哺乳动物胞质中的核酸可有效引起固有免疫反应,近年大量研究证实cGAS-cGAMP-STING信号通路在胞浆DNA识别和免疫防御激活过程中发挥关键作用。cGAS-cGAMP-STING信号通路的异常与肿瘤的发生发展密切相关,是药物研发的热门靶点。本研究利用稳定表达cGAS-STING通路的THP-1-Dual细胞和稳定敲除STING的THP-1 KO-STING细胞,建立了荧光素酶检测的STING激动剂筛选模型。进一步应用阳性药物验证了本模型的准确性和灵敏度,为高通量筛选STING激动剂提供了简便、高效、准确的筛选平台。

Tumor immunotherapy is a critical field in the development of anticancer drugs.The research of stimulator of interferon genes(STING)agonist provides a new idea for immunotherapy.Innate immune response can effectively be induced by nucleic acids in mammalian cytoplasm.In recent years,a large number of studies have confirmed that the cGAS-cGAMP-STING signaling pathway plays a key role in cytoplasmic DNA recognition and immune defense activation.The dysfunction of cGAS-cGAMP-STING is closely related to the tumorigenesis,and is a potent target for drug development.In this study,based on THP-1 dual cells which are stably expressing cGAS-STING pathway and THP-1 KO-STING cells which are stably depleted STING,a screening method for STING agonists was established by detection of luciferase.Furthermore,the accuracy and sensitivity of the model were verified using positive compound,providing a simple,efficient and accurate screening platform for highthroughput screening of STING agonists.