Simultaneous enhancement of cellular and humoral immunity by the lymph node-targeted cholesterolized TLR7 agonist liposomes  

作　　者：Dandan Wan Ziyi Bai Yu Zhang Li Chen Haiying Que Tianxia Lan Weiqi Hong Jiayu Huang Cai He Yuquan Wei Qiang Pu Xiawei Wei 

机构地区：[1]Laboratory of Aging Research and Cancer Drug Target,State Key Laboratory of Biotherapy and Cancer Center,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu 610041,China [2]Department of Thoracic Surgery,National Frontier Center of Disease Molecular Network,West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第10期4577-4590,共14页药学学报（英文版）

基　　金：supported by the National Science Foundation for Excellent Young Scholars(32122052,China);National Natural Science Foundation Regional Innovation and Development(No.U19A2003,China).

摘　　要：Toll-like receptor(TLR)agonists,as promising adjuvants and immunotherapeutic agents,have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways.However,their clinical application is hindered by uncontrolled systemic inflammatory reactions.Therefore,it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy.In this study,we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes(1V209-Cho-Lip^(+))to mitigate undesired side effects.Co-delivery of the model antigen OVA and cholesterolized TLR7 agonist facilitated DC maturation through TLR activation while ensuring optimal presentation of the antigen to CD8^(+)T cells.The main aim of the present study is to evaluate the adjuvant effectiveness of 1V209-Cho-Lip^(+)in tumor vaccines.Following immunization with 1V209-Cho-Lip^(+)+OVA,we observed a pronounced"depot effect"and enhanced trafficking to secondary lymphoid organs.Prophylactic vaccination with 1V209-Cho-Lip^(+)^(+)OVA significantly delays tumor development,prolongs mouse survival,and establishes durable immunity against tumor recurrence.Additionally,1V209-Cho-Lip^(+)+OVA,while used therapeutic tumor vaccine,has demonstrated its efficacy in inhibiting tumor progression,and when combined with anti-PD-1,it further enhances antitumor effects.Therefore,the co-delivery of antigen and lymph node-targeted cholesterolized TLR7 agonist shows great promise as a cancer vaccine.

关 键 词：TLR7 agonist Cationic liposomes Lymph node Cancer nanovaccines IMMUNOTHERAPY CROSS-PRESENTATION Cellular immunity Humoral immunity 

分 类 号：R730.51[医药卫生—肿瘤]