Nat. Biomed. Eng.: Oncolytic mineralized bacteria as potent locally administered immunotherapeutics

Title：

Oncolytic mineralized bacteria as potent locally administered immunotherapeutics

Authors：

Chenya Wang^1#, Liping Zhong^2#, Jiachen Xu³, Qi Zhuang¹, Fei Gong¹, Xiaojing Chen¹, Huiquan Tao⁴, Cong Hu², Fuquan Huang², Nailin Yang¹, Junyan Li¹, Qi Zhao,^1,4 Xinjun Sun², Yu Huo², Qian Chen¹, Yongxiang Zhao²*, Rui Peng¹*, Zhuang Liu^1,4*

Institutions：

¹Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China

²National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi, 530021, China

^{3Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China}

⁴InnoBM Pharmaceuticals Co. Ltd., Suzhou, Jiangsu, 215123, China

Abstract：

Oncolytic bacteria can trigger innate immune activity. However, the antitumour efficacy of inactivated bacteria is poor, and attenuated live bacteria pose substantial safety risks. Here we show that intratumourally injected paraformaldehyde-fixed bacteria coated with manganese dioxide potently activate innate immune activity, modulate the immunosuppressive tumou microenvironment and trigger tumour-specific immune responses and abscopal antitumour responses. A single intratumoural administration of mineralized Salmonella typhimurium suppressed the growth of multiple types of subcutaneous and orthotopic tumours in mice, rabbits and tree shrews and protected the cured animals against tumour rechallenge. We also show that mineralized bacteria can be administered via arterial embolization to treat orthotopic liver cancer in rabbits. Our findings support the further translational testing of oncolytic mineralized bacteria as potent and safe antitumour immunotherapeutics.

IF：

29.234

Link：

https://www.nature.com/articles/s41551-024-01191-w