Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy.
Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy.
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癌症免疫治疗中STING通路激活的化学和生物分子策略。
DOI：
10.1021/acs.chemrev.1c00750
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发表时间：
2022-03-23
期刊：
影响因子：
62.1
通讯作者：
Wilson JT
中科院分区：
文献类型：
--
作者：
Garland KM;Sheehy TL;Wilson JT
干扰素基因刺激因子（stimulator of interferon genes，STING）细胞信号通路是肿瘤免疫治疗的一个有前途的靶点。细胞内STING蛋白的活化触发多方面免疫刺激分子阵列的产生，其在适当的情况下可以驱动树突细胞成熟、抗肿瘤巨噬细胞极化、T细胞引发和活化、自然杀伤细胞活化、血管重编程和/或癌细胞死亡，导致免疫介导的肿瘤消除和抗肿瘤免疫记忆的产生。因此，有大量正在进行的临床前和临床研究，以进一步了解STING途径在癌症免疫监视中的作用，以及开发该途径的调节剂作为刺激抗肿瘤免疫的策略。然而，STING途径激动剂的功效受到许多药物递送和药理学挑战的限制。根据STING激动剂的类别和所需的施用途径，这些可能包括药物稳定性差、免疫细胞毒性、免疫相关不良事件、有限的肿瘤或淋巴结靶向和/或保留、低细胞摄取和细胞内递送以及对STING信号传导的幅度和动力学的复杂依赖性。本文综述了STING途径的简要概述，重点介绍了最近的生物学发展，免疫学后果和药物输送的影响。这篇综述还提供了一个不断扩大的化学策略，被用来提高疗效，安全性，和/或STING通路激动剂的临床效用的军火库的批判性分析，最后提请注意几个治疗进展的机会。
The stimulator of interferon genes (STING) cellular signaling pathway is a promising target for cancer immunotherapy. Activation of the intracellular STING protein triggers the production of a multifaceted array of immunostimulatory molecules, which, in the proper context, can drive dendritic cell maturation, antitumor macrophage polarization, T cell priming and activation, natural killer cell activation, vascular reprogramming, and/or cancer cell death, resulting in immune-mediated tumor elimination and generation of antitumor immune memory. Accordingly, there is a significant amount of ongoing preclinical and clinical research towards further understanding the role of the STING pathway in cancer immune surveillance as well as the development of modulators of the pathway as a strategy to stimulate antitumor immunity. Yet, the efficacy of STING pathway agonists is limited by many drug delivery and pharmacological challenges. Depending on the class of STING agonist and the desired administration route, these may include poor drug stability, immunocellular toxicity, immune-related adverse events, limited tumor or lymph node targeting and/or retention, low cellular uptake and intracellular delivery, and a complex dependence on the magnitude and kinetics of STING signaling. This review provides a concise summary of the STING pathway, highlighting recent biological developments, immunological consequences, and implications for drug delivery. This review also offers a critical analysis of an expanding arsenal of chemical strategies that are being employed to enhance the efficacy, safety, and/or clinical utility of STING pathway agonists and lastly draws attention to several opportunities for therapeutic advancements.
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影响因子：
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作者：
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作者：
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DOI：
10.1016/s0360-3016(02)03920-2
发表时间：
2002-12-01
影响因子：
7
作者：
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通讯作者：
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影响因子：
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作者：
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