Applied Microbiology and Biotechnology

, Volume 89, Issue 6, pp 1807–1819 | Cite as

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
Biotechnologically Relevant Enzymes and Proteins

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.

Keywords

Antitumor effects Tumor treatments TNF-α Salmonella typhimurium 

Supplementary material

253_2010_3006_MOESM1_ESM.doc (72 kb)
Fig. S1Survival of recombinant bacteria in tumor-bearing mice. B16F10 tumor-bearing C57BL6 mice were subcutaneously inoculated with 1 × 108S. typhimurium harboring TNF-α next to tumor. At 1, 12, and 24 h after treatment, the tumor region was homogenized. Tumor cell lysates were cultivated and the percent survival of recombinant bacteria was calculated. (DOC 71 kb)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Won Suck Yoon
    • 1
    • 2
  • Yang Seok Chae
    • 3
  • Juyeon Hong
    • 4
  • Yong Keun Park
    • 1
  1. 1.Department of Biotechnology, School of Life Sciences and BiotechnologyKorea UniversitySeoulRepublic of Korea
  2. 2.Office of ResearchKorea UniversitySeoulRepublic of Korea
  3. 3.Department of Pathology, Korea University College of MedicineKorea UniversitySeoulRepublic of Korea
  4. 4.Rice UniversityHoustonUSA

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