The first immunotherapeutic agent in human history was Coley’s toxins, discovered in the 19th century. Over the past decade, bacteria-based tumour therapies have regained research interest, usually through genetic engineering of bacteria to reduce their virulence and equip them with additional anti-tumour abilities. However, although inactivated bacteria showed limited antitumor efficacy, attenuated bacteria often possess safety risks with narrow therapeutic windows.
Recently, Prof. Zhuang Liu and Prof. Rui Peng from the Institute of Functional Nano and Soft Materials at Soochow University and Prof. Yongxiang Zhao fromGuangxi Medical Universityhavedeveloped mineralized bacteria by growth of MnO2nanostructures on the surface of fixed bacteria. Selecting MnO2-coated fixedS. typhimurium(M@FS) as the optimal agent, they found that single intratumoral administration of M@FS resulted in surprisingly strong efficacies in suppressing various types of mouse tumor models and a rabbit cancer model, and the cured animals gained immune memory to reject re-challenged tumours. An abscopal antitumor effect was also observed, indicating systemic antitumor immunity. The antitumor mechanisms of M@F.S were preliminarily demonstrated to be innate immune activation followed by subsequent activation of tumor-specific immune responses, together with the modulation of immunosuppressive tumor microenvironment. They further reported the efficacy of biomineralized bacteria in inhibiting an orthotopic breast tumour model established on tree shrews, an alternative animal model to primates with a more clinically relevant tumor model. After M@FS treatment, two out of six tree shrews have been cancer-free without recurrence. Beyond intratumoral injection, the biomineralized bacteria could also be employed as a potent therapeutic agent for interventional transarterial immuno-embolization (TAIE) therapy to treat orthotopic liver cancer. Such oncolytic mineralized bacteria could therefore offer a new type of potent yet safe immunotherapeutic strategy against various types of solid tumours with great clinical potentials.
The above research has been published online in Nature Biomedical Engineering (DOI: 10.1038/s41551-024-01191-w).
Link to paper:https://www.nature.com/articles/s41551-024-01191-w
Title:Oncolytic mineralized bacteria as potent locally administered immunotherapeutics
Authors:Chenya Wang, Liping Zhong, Jiachen Xu, Qi Zhuang, Fei Gong, Xiaojing Chen, Huiquan Tao, Cong Hu, Fuquan Huang, Nailin Yang, Junyan Li, Qi Zhao, Xinjun Sun, Yu Huo, Qian Chen, Yongxiang Zhao*, Rui Peng*, Zhuang Liu*
Editor: Guo Jia