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

Authors
 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 
Citation
 EUROPEAN JOURNAL OF CANCER, Vol.70 : 48-61, 2017 
Journal Title
 EUROPEAN JOURNAL OF CANCER 
ISSN
 0959-8049 
Issue Date
2017
MeSH
Animals ; Blotting, Western/methods ; Disease Models, Animal ; Humans ; Immunity, Innate ; Immunotherapy/methods* ; Interferon-gamma/biosynthesis* ; Killer Cells, Natural/immunology ; Macrophages/metabolism ; Melanoma, Experimental/therapy* ; Mice ; Mice, Inbred C57BL ; Organisms, Genetically Modified/metabolism* ; Salmonella typhimurium/metabolism* ; Salmonella typhimurium/pathogenicity ; Skin Neoplasms/therapy* ; Tumor Cells, Cultured
Keywords
Genetically modified Salmonella typhimurium (S. typhimurium) ; Interferon-gamma (IFN-γ) ; Melanoma ; SipB160 ; Treatment option for melanoma
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0959804916324947
DOI
10.1016/j.ejca.2016.10.010.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Byeong Mo(김병모) ORCID logo https://orcid.org/0000-0002-0582-3132
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154174
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