In situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases  

作　　者：Yuan Li Fan Tong Yufan Wang Jing Wang Manqi Wu Hanmei Li Hongyan Guo Huile Gao 

机构地区：[1]Department of Obstetrics and Gynecology,National Clinical Research Center for Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China [2]Key Laboratory of Drug Targeting and Drug Delivery Systems,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [3]School of Food and Biological Engineering,Chengdu University,Chengdu 610106,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第9期4102-4117,共16页药学学报（英文版）

基　　金：the National Natural Science Foundation of China(No.82102769);the 111 Project(No.B18035,China);the Fundamental of Research Funds for the Central Universities and Beijing Natural Science Foundation(No.L212054,China).

摘　　要：Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with [e-mail] from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.

关 键 词：In situ nano-vaccine Lymph node targeting MMP-2 responsive PD-1 Combination therapy CPG Ovarian cancer METASTASES 

分 类 号：R730.51[医药卫生—肿瘤] R186[医药卫生—临床医学]