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靶向Toll样受体7/8疗法的最新发展趋势。

Recent trends in the development of Toll-like receptor 7/8-targeting therapeutics.

作者信息

Huang Xuan, Zhang Xiaoyong, Lu Mengji

机构信息

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Institute of Virology, University Hospital of Essen, Essen, Germany.

出版信息

Expert Opin Drug Discov. 2021 Aug;16(8):869-880. doi: 10.1080/17460441.2021.1898369. Epub 2021 Mar 15.

DOI:10.1080/17460441.2021.1898369
PMID:33678093
Abstract

: Toll-like receptor (TLR) 7 and TLR8 are functionally localized to endosomes and recognize specific RNA sequences. They play crucial roles in initiating innate and adaptive immune responses. TLR7/8 activation protects the host against invading pathogens and enhances immune responses. In contrast, sustained TLR7/8 signaling leads to immune overreaction. Therefore, agonists or antagonists targeting TLR7/8 signaling are favorable drug candidates for the treatment of immune disorders.: Basic knowledge about TLR7 and TLR8 and their signaling pathways are briefly reviewed. Various therapeutic agents have been designed to activate or antagonize TLR7/8 signaling pathways, and their safety and efficacy for the treatment of multiple diseases have been investigated in preclinical animal models and clinical trials. TLR7/8 agonists exhibit potent antiviral activity and regulate anti-tumor immune responses. TLR7 agonists have also been used as adjuvants to improve vaccine immunogenicity and generate greater seroprotection. TLR7/8 antagonists are promising candidates for the treatment of autoimmune and inflammatory diseases.: TLR7/8 pathways are favorable targets for immunological therapies. Future research should concentrate on the optimization of drug safety, efficiency, and specificity. Detailed mechanistic studies will contribute to the development of TLR7/8 immunomodulators and novel therapeutic strategies.

摘要

Toll样受体(TLR)7和TLR8在功能上定位于内体,并识别特定的RNA序列。它们在启动先天性和适应性免疫反应中发挥关键作用。TLR7/8激活可保护宿主抵御入侵病原体并增强免疫反应。相反,持续的TLR7/8信号传导会导致免疫反应过度。因此,靶向TLR7/8信号传导的激动剂或拮抗剂是治疗免疫紊乱的理想候选药物。

简要回顾了关于TLR7和TLR8及其信号通路的基础知识。已经设计了各种治疗剂来激活或拮抗TLR7/8信号通路,并且已经在临床前动物模型和临床试验中研究了它们治疗多种疾病的安全性和有效性。TLR7/8激动剂表现出强大的抗病毒活性并调节抗肿瘤免疫反应。TLR7激动剂也已被用作佐剂来提高疫苗免疫原性并产生更大的血清保护作用。TLR7/8拮抗剂是治疗自身免疫性和炎性疾病的有希望的候选药物。

TLR7/8通路是免疫治疗的有利靶点。未来的研究应集中在优化药物安全性、有效性和特异性上。详细的机制研究将有助于开发TLR7/8免疫调节剂和新的治疗策略。

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