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

Won Suck Yoon, Yang Seok Chae, Juyeon Hong, Yong Keun Park

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1807-1819
Number of pages13
JournalApplied Microbiology and Biotechnology
Volume89
Issue number6
DOIs
Publication statusPublished - 2011 Mar

Keywords

  • Antitumor effects
  • Salmonella typhimurium
  • TNF-α
  • Tumor treatments

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

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