Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Phase I Clinical Trails Center, The First Hospital, China Medical University, 518 North Chuangxin Road, Baita Street, Hunnan District, Shenyang, 110102 Liaoning, China.
Nano Lett. 2022 Jun 22;22(12):5055-5064. doi: 10.1021/acs.nanolett.2c00699. Epub 2022 May 18.
Oncolytic viruses (OVs) have been widely used as anticancer therapeutics because of their systemic immune responses during viral replication. However, the low enrichment of OVs within tumors and limited immune activation have hindered their clinical application. Herein, we proposed the concept of bacteria-assisted targeting of OVs to tumors, with liposome-cloaked oncolytic adenoviruses (OAs) conjugated onto tumor-homing BL21 (designated as -lipo-OAs) for enhanced cancer immunotherapy. Notably, the enrichment of OAs transported by self-propelled bacterial microbe vehicles in -lipo-OAs in a nonsmall cell lung tumor can be potentiated by more than 170-fold compared with that of intravenously injected bare OAs. studies further revealed that -lipo-OAs administered intravenously significantly enhanced antitumor immunity through bacterial-viral-augmented immune responses. Our findings suggest that the self-driving microbe vehicle as a systemic delivery system for OVs can be a potent platform for developing future anticancer biotherapeutics at the clinical level.
溶瘤病毒 (OVs) 因其在病毒复制过程中的全身免疫反应而被广泛用作抗癌治疗剂。然而，OVs 在肿瘤内的低富集和有限的免疫激活限制了它们的临床应用。在此，我们提出了细菌辅助靶向肿瘤 OVs 的概念，即用脂质体包裹的溶瘤腺病毒 (OAs) 与肿瘤归巢 BL21 连接（命名为-lipo-OAs），以增强癌症免疫治疗。值得注意的是，与静脉注射的裸 OAs 相比，-lipo-OAs 中由自行推进的细菌微生物载体运输的 OAs 的富集可增强 170 多倍。研究进一步表明，静脉注射-lipo-OAs 通过细菌-病毒增强的免疫反应显著增强了抗肿瘤免疫。我们的研究结果表明，作为 OVs 的系统递送系统的自驱动微生物载体可以成为在临床水平上开发未来抗癌生物疗法的有力平台。
