Antitumor therapeutic effects of a genetically engineered Salmonella typhimurium harboring TNF-alpha in mice

Abstract

Although the use of TNF-alpha 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-alpha. 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-alpha 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-alpha, and induced apoptosis of tumor cells without apparent side effects. In a murine melanoma model, the bacterial capsule of TNF-alpha 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-alpha were also observed in cervical cancer, melanoma, breast cancer, colon cancer, and renal carcinoma. These results suggest that the bacterial capsule of TNF-alpha is a promising strategy for TNF-alpha treatment.