自噬
溶瘤病毒
癌症免疫疗法
溶癌病毒
肿瘤微环境
免疫疗法
癌细胞
免疫原性细胞死亡
免疫系统
癌症研究
化学
癌症
生物
细胞凋亡
免疫学
生物化学
遗传学
作者
Weiyue Ban,Mengchi Sun,Hanwei Huang,Wanxu Huang,Siwei Pan,Pengfei Liu,B. Li,Zhenguo Cheng,He Zhang,Funan Liu,Jin Sun
标识
DOI:10.1038/s41467-023-38679-z
摘要
Oncolytic adenovirus (Ad) infection promotes intracellular autophagy in tumors. This could kill cancer cells and contribute to Ads-mediated anticancer immunity. However, the low intratumoral content of intravenously delivered Ads could be insufficient to efficiently activate tumor over-autophagy. Herein, we report bacterial outer membrane vesicles (OMVs)-encapsulating Ads as microbial nanocomposites that are engineered for autophagy-cascade-augmented immunotherapy. Biomineral shells cover the surface antigens of OMVs to slow their clearance during in vivo circulation, enhancing intratumoral accumulation. After entering tumor cells, there is excessive H2O2 accumulation through the catalytic effect of overexpressed pyranose oxidase (P2O) from microbial nanocomposite. This increases oxidative stress levels and triggers tumor autophagy. The autophagy-induced autophagosomes further promote Ads replication in infected tumor cells, leading to Ads-overactivated autophagy. Moreover, OMVs are powerful immunostimulants for remolding the immunosuppressive tumor microenvironment, facilitating antitumor immune response in preclinical cancer models in female mice. Therefore, the present autophagy-cascade-boosted immunotherapeutic method can expand OVs-based immunotherapy.
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