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

13 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

Fingerprint

Salmonella typhimurium
Interferons
Melanoma
Neoplasms
Salmonella
Interferon-gamma
Therapeutics
Growth
Inbred C57BL Mouse
Natural Killer Cells
Immunity
Phosphates

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yoon, Wonsuck ; Park, Yoo Chang ; Kim, Jinseok ; Chae, Yang Seok ; Byeon, Jung Hye ; Min, Sang Hyun ; Park, Sungha ; Yoo, Young ; Park, Yong Keun ; Kim, Byeong Mo. / Application of genetically engineered Salmonella typhimurium for interferon-gamma–induced therapy against melanoma. In: European Journal of Cancer. 2017 ; Vol. 70. pp. 48-61.
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Application of genetically engineered Salmonella typhimurium for interferon-gamma–induced therapy against melanoma. / Yoon, Wonsuck; Park, Yoo Chang; Kim, Jinseok; Chae, Yang Seok; Byeon, Jung Hye; Min, Sang Hyun; Park, Sungha; Yoo, Young; Park, Yong Keun; Kim, Byeong Mo.

In: European Journal of Cancer, Vol. 70, 01.01.2017, p. 48-61.

Research output: Contribution to journalArticle

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