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Harnessing cGAS-STING Pathway for Cancer Immunotherapy: From Bench to Clinic
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2022-07-06 , DOI: 10.1002/adtp.202200040
DaeYong Lee 1 , Kristin Huntoon 1 , Minjeong Kang 2 , Yifei Lu 1 , Thomas Gallup 1 , Wen Jiang 2 , Betty Y S Kim 1
Affiliation  

Recent advances in cancer immunotherapy have accomplished clinical successes in certain cancer models over the past decade. However, cancer treatments with adoptive cell transfer or immune checkpoint blockade (ICB) have shown critical limitations against solid tumors, which comprise the majority of human cancers. Thus, novel cancer immunotherapy which harnesses innate immunity process may be required in these tumor types. Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, one of the innate immune sensors, has gained interest in the field of immuno-oncology as activation of this pathway can drive both innate and adaptive immune responses among immunosuppressive tumor microenvironments. Recently, various cGAS-STING-activating strategies have been intensively investigated to achieve durable and widespread therapeutic responses in in vivo models. These meaningful preclinical outcomes have enabled several clinical trials. This review discusses agents targeting various aspects of the cGAS-STING pathway in cancer immunotherapy from benchtop to bedside. Moreover, various approaches to improve the clinical feasibility of cGAS-STING-activating strategies are delineated.

中文翻译:

利用 cGAS-STING 途径进行癌症免疫治疗:从实验室到临床

在过去十年中,癌症免疫疗法的最新进展在某些癌症模型中取得了临床成功。然而,采用过继细胞转移或免疫检查点阻断 (ICB) 的癌症治疗已显示出对实体瘤的严重限制,实体瘤构成了人类癌症的大多数。因此,在这些肿瘤类型中可能需要利用先天免疫过程的新型癌症免疫疗法。环状 GMP-AMP 合酶 (cGAS) - 干扰素基因刺激物 (STING) 通路是先天免疫传感器之一,在免疫肿瘤学领域引起了人们的兴趣,因为该通路的激活可以驱动免疫抑制中的先天和适应性免疫反应。肿瘤微环境。最近,已经深入研究了各种 cGAS-STING 激活策略,以在体内模型中实现持久和广泛的治疗反应。这些有意义的临床前结果使多项临床试验成为可能。本综述讨论了从台式到床边的癌症免疫治疗中针对 cGAS-STING 通路各个方面的药物。此外,还描述了提高 cGAS-STING 激活策略临床可行性的各种方法。
更新日期:2022-07-06
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