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STING 通路的药理学调节在癌症免疫治疗中的作用。

Pharmacological Modulation of the STING Pathway for Cancer Immunotherapy.

机构信息

Microbiology, Bioorganic and Macromolecular Chemistry, Faculty of Pharmacy, Université libre de Bruxelles, Boulevard du Triomphe, 1050 Brussels, Belgium; Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Microbiology, Bioorganic and Macromolecular Chemistry, Faculty of Pharmacy, Université libre de Bruxelles, Boulevard du Triomphe, 1050 Brussels, Belgium.

出版信息

Trends Mol Med. 2019 May;25(5):412-427. doi: 10.1016/j.molmed.2019.02.007. Epub 2019 Mar 15.

Abstract

The advent of immunotherapy in recent years has shown the potential to revolutionize the treatment of cancer. Unleashing antitumor T cell responses via immune checkpoint blockade has led to remarkable responses in previously untreatable tumors. The master regulator of interferon-mediated antiviral responses - stimulator of interferon genes (STING) - has now emerged as a critical mediator of innate immune sensing of cancer, and is a promising target for local immunostimulation, promoting intratumoral inflammation, and facilitating antitumor T cell responses. Pharmacological activation of the STING pathway can lead to T cell-mediated tumor regression in preclinical tumor models, and novel STING activating small molecules are now being tested in clinical trials. Here we will introduce the STING pathway and review the current state of drug development.

摘要

近年来免疫疗法的出现显示出了彻底改变癌症治疗的潜力。通过免疫检查点阻断来释放抗肿瘤 T 细胞反应,已经导致以前无法治疗的肿瘤出现了显著的反应。干扰素介导的抗病毒反应的主调节因子——干扰素基因刺激因子 (STING)——现在已成为癌症固有免疫感应的关键介质,是局部免疫刺激的有前途的靶点,可促进肿瘤内炎症,并促进抗肿瘤 T 细胞反应。STING 途径的药理学激活可导致临床前肿瘤模型中的 T 细胞介导的肿瘤消退,并且新型 STING 激活小分子正在临床试验中进行测试。在这里,我们将介绍 STING 途径,并回顾药物开发的现状。

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