title: Application of genetically engineered Salmonella typhimurium for interferon-gamma-induced therapy against 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.
authors.affiliation: Allergy Immunology Center, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
authors.forename: Wonsuck
authors.initials: W
authors.lastname: Yoon
authors.affiliation: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
authors.forename: Yoo Chang
authors.initials: YC
authors.lastname: Park
authors.affiliation: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
authors.forename: Jinseok
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
authors.forename: Yang Seok
authors.initials: YS
authors.lastname: Chae
authors.affiliation: Department of Pediatrics, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Byeon
authors.affiliation: New Drug Development Center, DGMIF, 80 Cheombok-ro, Dong-gu, Daegu 41061, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Min
authors.affiliation: Division of Cardiology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.affiliation: Allergy Immunology Center, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; Department of Pediatrics, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Yoo
authors.affiliation: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea. Electronic address: ykpark@korea.ac.kr.
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Park
authors.affiliation: Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. Electronic address: bkim2@yuhs.ac.
authors.forename: Byeong Mo
authors.initials: BM
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D030781:Organisms, Genetically Modified / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000378:metabolism* / Q000472:pathogenicity; D012878:Skin Neoplasms / Q000628:therapy*; D014407:Tumor Cells, Cultured
chemical_list: D007371:Interferon-gamma
keywords: Genetically modified Salmonella typhimurium (S. typhimurium); Interferon-gamma (IFN-γ); Melanoma; SipB160; Treatment option for melanoma