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

作者机构：State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2023年第13卷第2期

页      面：804-818页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

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) 

主　　题：Neoadjuvant Chemotherapy Immunotherapy Mitoxantrone Vaccine Azobenzene derivatives Reduction responsive Melanoma 

摘      要：Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers,which benefits from tumor ***,the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and ***,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 *** 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 ***,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 ***,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.