A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence.
10.1016/j.apsb.2022.09.017
- Author:
Tao HE
1
;
Mingxing HU
1
;
Shunyao ZHU
1
;
Meiling SHEN
1
;
Xiaorong KOU
1
;
Xiuqi LIANG
1
;
Lu LI
1
;
Xinchao LI
1
;
Miaomiao ZHANG
1
;
Qinjie WU
1
;
Changyang GONG
1
Author Information
1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- Keywords:
Azobenzene derivatives;
Chemotherapy;
Immunotherapy;
Melanoma;
Mitoxantrone;
Neoadjuvant;
Reduction responsive;
Vaccine
- From:
Acta Pharmaceutica Sinica B
2023;13(2):804-818
- CountryChina
- Language:English
-
Abstract:
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.
