Antitumor therapeutic effects of a genetically engineered Salmonella typhimurium harboring TNF-α in mice.
Although the use of TNF-α in the treatment of cancer is restricted due to its non-specific cytotoxicity and narrow range of applications to different cancers in clinical trials, we investigated a safe anti-cancer drug by the use of engineered bacterial capsule harboring TNF-α. The engineered bacterial capsule was designed to target cancer cells, promote a tumor-suppressive environment, and increase the efficacy of existing cancer treatments, including chemotherapy, radiotherapy, and cell therapy. The engineered bacterial capsule was constructed with Salmonella capsulizing TNF-α protein, which was produced and capsulized by Salmonella to reduce side effects of the protein. This bacterial capsule induced a tumor-suppressive environment through the activation of natural killer cells. Engineered bacterial capsule invaded tumor cells, released TNF-α, and induced apoptosis of tumor cells without apparent side effects. In a murine melanoma model, the bacterial capsule of TNF-α significantly inhibited tumor growth by 80-100% and prolonged the survival of the mice. When tested in combination with chemotherapy (cisplatin), antibiotics, and vaccine, recombinant microbial treatment increased the anti-tumor effects of existing therapies. The anti-tumor effects of the bacterial capsule of TNF-α were also observed in cervical cancer, melanoma, breast cancer, colon cancer, and renal carcinoma. These results suggest that the bacterial capsule of TNF-α is a promising strategy for TNF-α treatment.
Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Won Suck
WS
Yoon
Yang Seok
YS
Chae
Juyeon
J
Hong
Yong Keun
YK
Park
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D007694:Killer Cells, Natural / Q000276:immunology; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha