Application of genetically engineered Salmonella typhimurium for interferon-gamma-induced therapy against melanoma
- Authors
- 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
- Issue Date
- 1월-2017
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Genetically modified Salmonella typhimurium (S. typhimurium); Interferon-gamma (IFN-gamma); SipB160; Melanoma; Treatment option for melanoma
- Citation
- EUROPEAN JOURNAL OF CANCER, v.70, pp.48 - 61
- Indexed
- SCIE
SCOPUS
- Journal Title
- EUROPEAN JOURNAL OF CANCER
- Volume
- 70
- Start Page
- 48
- End Page
- 61
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/85003
- DOI
- 10.1016/j.ejca.2016.10.010
- ISSN
- 0959-8049
- 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-gammS. 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-gamma), showed little toxicity to normal tissues with no observable adverse effects. However, S. typhimurium (IFN-gamma)-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-gamma) has potential for melanoma treatment. (C) 2016 Elsevier Ltd. All rights reserved.a (IFN-gamma) as a tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-gamma was fused to the N-terminal region (residues 1e160) of SipB (SipB160) for secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant IFN-gamma (S. typhimurium (IFN-gamma)) invaded the melanoma cells and induced cytotoxicity. Subcutaneous administration of S. typhimurium (IFN-gamma) 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-gamma), showed little toxicity to normal tissues with no observable adverse effects. However, S. typhimurium (IFN-gamma)-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-gamma) has potential for melanoma treatment. (C) 2016 Elsevier Ltd. All rights reserved.
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