title: Angiogenic inhibitors delivered by the type III secretion system of tumor-targeting Salmonella typhimurium safely shrink tumors in mice.
abstract: Despite of a growing number of bacterial species that apparently exhibit intrinsic tumor-targeting properties, no bacterium is able to inhibit tumor growth completely in the immunocompetent hosts, due to its poor dissemination inside the tumors. Oxygen and inflammatory reaction form two barriers and restrain the spread of the bacteria inside the tumors. Here, we engineered a Salmonella typhimurium strain named ST8 which is safe and has limited ability to spread beyond the anaerobic regions of tumors. When injected systemically to tumor-bearing immunocompetent mice, ST8 accumulated in tumors at levels at least 100-fold greater than parental obligate anaerobic strain ST4. ST8/pSEndo harboring therapeutic plasmids encoding Endostatin fused with a secreted protein SopA could target vasculature at the tumor periphery, can stably maintain and safely deliver a therapeutic vector, release angiogenic inhibitors through a type III secretion system (T3SS) to interfere with the pro-angiogenic action of growth factors in tumors. Mice with murine CT26 colon cancer that had been injected with ST8/pSEndo showed efficient tumor suppression by inducing more severe necrosis and inhibiting blooding vessel density within tumors. Our findings provide a therapeutic platform for indirectly acting therapeutic strategies such as anti-angiogenesis and immune therapy.
authors: Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, L3-72, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong.|Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, People's Republic of China.
authors: Lei
authors: L
authors: Shi
authors: Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, L3-72, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong.|Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, People's Republic of China.|Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, People's Republic of China.
authors: Bin
authors: B
authors: Yu
authors: Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam, Hong Kong.|Advanced Institute of Translational Medicine, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors: Chun-Hui
authors: CH
authors: Cai
authors: Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, L3-72, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong. jdhuang@hku.hk.|Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, People's Republic of China. jdhuang@hku.hk.|The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen, People's Republic of China. jdhuang@hku.hk.
authors: Jian-Dong
authors: JD
authors: Huang
keywords: Anti-angiogenesis; Bacterial cancer therapy; Salmonella typhimurium; Tumor-targeting; Type III secretion system; Viable region