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.

溶瘤腺病毒 (Ad) 感染促进肿瘤细胞内自噬。这可以杀死癌细胞并有助于 Ads 介导的抗癌免疫。然而，静脉内递送的 Ads 的低瘤内含量可能不足以有效激活肿瘤过度自噬。在此，我们报告了细菌外膜囊泡 (OMV) 封装的 Ads 作为微生物纳米复合材料，专为自噬级联增强免疫疗法而设计。生物矿物壳覆盖 OMV 的表面抗原，以减缓它们在体内循环过程中的清除，增强肿瘤内积累。进入肿瘤细胞后，通过过_{表达的吡喃}糖氧化酶（P ₂O) 来自微生物纳米复合材料。这会增加氧化应激水平并触发肿瘤自噬。自噬诱导的自噬体进一步促进受感染肿瘤细胞中的 Ads 复制，导致 Ads 过度激活的自噬。此外，OMV 是强大的免疫刺激剂，可重塑免疫抑制性肿瘤微环境，促进雌性小鼠临床前癌症模型中的抗肿瘤免疫反应。因此，目前的自噬级联增强免疫治疗方法可以扩展基于 OVs 的免疫治疗。