首页|CASTING:A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

CASTING:A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recog-nized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase Ⅰ clinical trials as a mono-therapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally de-sign a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue reten-tion.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More important-ly,CASTING displays a superior adjuvant activity on SARS-CoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.

STING agonistcyclic dinucleotidescali-xarenesupramolecular deliverycancer immuno-therapySARS-CoV-2 vaccineadjuvant

Jun-Jun Wu、Fang-Yuan Chen、Bei-Bei Han、Hong-Qing Zhang、Lang Zhao、Zhe-Rui Zhang、Juan-Juan Li、Bo-Dou Zhang、Ya-Nan Zhang、Yu-Xin Yue、Hong-Guo Hu、Wen-Hao Li、Bo Zhang、Yong-Xiang Chen、Dong-Sheng Guo、Yan-Mei Li

展开 >

Key Lab of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education),Department of Chemistry,Center for Synthetic and Systems Biology,Tsinghua University,Beijing 100084

Key Laboratory of Innate Immune Biology of Fujian Province,Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation,Biomedical Research Center of South China,College of Life Sciences,Fujian Normal University,Fuzhou 350117

College of Chemistry,Key Laboratory of Functional Polymer Materials,Ministry of Education,State Key Laboratory of Elemento-Organic Chemistry,Nankai University,Tianjin 300071

Key Laboratory of Special Pathogens and Biosafety,Center for Emerging Infectious Diseases,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071

University of Chinese Academy of Sciences,Beijing 100049

Beijing Institute for Brain Disorders,Beijing 100069

展开 >

国家重点研发计划国家重点研发计划Tsinghua University Spring Breeze Fund国家自然科学基金国家自然科学基金NCC Fund

2019YFA09042002018YFA05076002020Z99CFY0429205310831961143004NCC2020FH04

2023

10.31635/ccschem.022.202201859

中国化学会会刊(英文)

中国化学会会刊(英文)

CSCD
ISSN：
年,卷(期)：2023.5(4)
  • 56