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

Won Suck Yoon1, Yang Seok Chae, Juyeon Hong

  • 1Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.

Insights

Engineered bacterial capsules carrying tumor necrosis factor-alpha (TNF-α) offer a targeted cancer therapy. This novel approach reduces side effects and enhances existing treatments, showing significant tumor inhibition in preclinical models.

Area of Science:

  • Oncology
  • Microbiology
  • Immunology

Background:

  • Tumor necrosis factor-alpha (TNF-α) has limited clinical use in cancer due to toxicity and narrow efficacy.
  • Targeted delivery systems are needed to improve TNF-α's therapeutic index for cancer treatment.

Purpose of the Study:

  • To develop and evaluate an engineered bacterial capsule system for targeted delivery of TNF-α.
  • To assess the safety and efficacy of this system in promoting a tumor-suppressive environment and enhancing anti-cancer therapies.

Main Methods:

  • Construction of Salmonella bacterial capsules engineered to encapsulate and release TNF-α protein.
  • Evaluation of the bacterial capsule's ability to target cancer cells, activate natural killer cells, and induce tumor cell apoptosis.
  • Assessment of anti-tumor efficacy in a murine melanoma model, both as monotherapy and in combination with chemotherapy, antibiotics, and vaccines.
  • Testing in various cancer types including cervical cancer, melanoma, breast cancer, colon cancer, and renal carcinoma.

Main Results:

  • The engineered bacterial capsule effectively delivered TNF-α, inducing apoptosis in tumor cells with reduced side effects.
  • Significant tumor growth inhibition (80-100%) and prolonged survival were observed in a murine melanoma model.
  • Combination therapy demonstrated enhanced anti-tumor effects compared to existing treatments.
  • Anti-tumor activity was confirmed across multiple cancer types.

Conclusions:

  • Engineered bacterial capsules offer a promising, safe, and effective strategy for targeted TNF-α delivery in cancer therapy.
  • This approach enhances the efficacy of conventional cancer treatments and warrants further clinical investigation.