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Recent trends in the development of Toll-like receptor 7/8-targeting therapeutics
Xuan Huang, Xiaoyong Zhang & Mengji Lu
Received 30 Jul 2020, Accepted 01 Mar 2021, Accepted author version posted online: 07 Mar 2021
Download citation https://doi.org/10.1080/17460441.2021.1898369 CrossMark Logo CrossMark
Accepted author version
Abstract
Introduction: Toll-like receptor (TLR) 7 and TLR8 are functionally localized to endosomes and recognize specific RNA sequences. They have 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.
Areas covered: 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.
Expert opinion: 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.
Keywords: agonistantagonistclinical trialinnate immunitytoll-like receptor 7/8
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Acknowledgments
The authors acknowledge Dr. Yin Wu for his assistance in data collection.
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Toll-like receptor (TLR) 7 and TLR8 are closely related members of the TLR family. They are sensors of single-stranded ribonucleic acids from endosomal compartments and nucleoside-based molecules.
TLR7 activates plasmacytoid dendritic cells and leads to production of type I interferon. TLR8 is mainly expressed on myeloid dendritic cells, monocytes, and macrophages and induces secretion of proinflammatory cytokines.
TLR7 and TLR8 are important regulators of innate and adaptive immune responses, therefore representing potential targets for immune therapy.
TLR7/8 agonists have been evaluated in various diseases associated with deficient immune responses such as chronic viral infections, cancers, and allergic diseases, and in vaccine studies. Safety and efficacy have been demonstrated in several studies.
TLR7/8 antagonists have mainly been studied in autoimmune and inflammatory diseases. Such agents were safe and significantly downregulated the expression of inflammation-related cytokines. |
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发表于 2021-3-9 19:29