Application of genetically engineered Salmonella typhimurium for interferon-gamma–induced therapy against melanoma

Wonsuck Yoon, Yoo Chang Park, Jinseok Kim, Yang Seok Chae, Jung Hye Byeon, Sang Hyun Min, Sungha Park, Young Yoo, Yong Keun Park, Byeong Mo Kim

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Salmonella have been experimentally used as anti-cancer agents, because they show selective growth in tumours. In this study, we genetically modified attenuated Salmonella typhimurium to express and secrete interferon-gamma (IFN-γ) as a tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-γ was fused to the N-terminal region (residues 1–160) of SipB (SipB160) for secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant IFN-γ (S. typhimurium (IFN-γ)) invaded the melanoma cells and induced cytotoxicity. Subcutaneous administration of S. typhimurium (IFN-γ) also efficiently inhibited tumour growth and prolonged the survival of C57BL/6 mice bearing B16F10 melanoma compared with administration of phosphate-buffered saline (PBS), unmodified S. typhimurium or S. typhimurium expressing empty vector (S. typhimurium [Vec]) in a natural killer (NK) cell-dependent manner. Moreover, genetically modified Salmonella, including S. typhimurium (IFN-γ), showed little toxicity to normal tissues with no observable adverse effects. However, S. typhimurium (IFN-γ)-mediated tumour suppression was attributed to direct killing of tumour cells rather than to stable anti-tumour immunity. Collectively, these results suggest that tumour-targeted therapy using S. typhimurium (IFN-γ) has potential for melanoma treatment.

Original languageEnglish
Pages (from-to)48-61
Number of pages14
JournalEuropean Journal of Cancer
Volume70
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • Genetically modified Salmonella typhimurium (S. typhimurium)
  • Interferon-gamma (IFN-γ)
  • Melanoma
  • SipB160
  • Treatment option for melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Yoon, W., Park, Y. C., Kim, J., Chae, Y. S., Byeon, J. H., Min, S. H., Park, S., Yoo, Y., Park, Y. K., & Kim, B. M. (2017). Application of genetically engineered Salmonella typhimurium for interferon-gamma–induced therapy against melanoma. European Journal of Cancer, 70, 48-61. https://doi.org/10.1016/j.ejca.2016.10.010