A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence  

作　　者：Tao He Mingxing Hu Shunyao Zhu Meiling Shen Xiaorong Kou Xiuqi Liang Lu Li Xinchao Li Miaomiao Zhang Qinjie Wu Changyang Gong 

机构地区：[1]State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第2期804-818,共15页药学学报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(82172094);Funds of Sichuan Province for Distinguished Young Scholar(2021JDJQ0037,China);1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYYC08002,China)。

摘　　要：Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers,which benefits from tumor downstaging.However,the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence.Herein,a tactical nanomissile(TALE),equipped with a guidance system(PD-L1 monoclonal antibody),ammunition(mitoxantrone,Mit),and projectile bodies(tertiary amines modified azobenzene derivatives),is designed as a neoadjuvant chemo-immunotherapy setting,which aims at targeting tumor cells,and fast-releasing Mit owing to the intracellular azoreductase,thereby inducing immunogenic tumor cells death,and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system.The formed in situ tumor vaccine can recruit and activate antigen-presenting cells,and ultimately increase the infiltration of CD8^(+)T cells while reversing the immunosuppression microenvironment.Moreover,this approach provokes a robust systemic immune response and immunological memory,as evidenced by preventing 83.3%of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model.Collectively,our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

关 键 词：NEOADJUVANT Chemotherapy Immunotherapy MITOXANTRONE Vaccine Azobenzene derivatives Reduction responsive MELANOMA 

分 类 号：R730.5[医药卫生—肿瘤]