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 language | English |
|---|---|
| Pages (from-to) | 48-61 |
| Number of pages | 14 |
| Journal | European Journal of Cancer |
| Volume | 70 |
| DOIs | |
| Publication status | Published - 2017 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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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 journal › Article
TY - JOUR
T1 - Application of genetically engineered Salmonella typhimurium for interferon-gamma–induced therapy against melanoma
AU - Yoon, Wonsuck
AU - Park, Yoo Chang
AU - Kim, Jinseok
AU - Chae, Yang Seok
AU - Byeon, Jung Hye
AU - Min, Sang Hyun
AU - Park, Sungha
AU - Yoo, Young
AU - Park, Yong Keun
AU - Kim, Byeong Mo
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84996619330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84996619330&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2016.10.010
DO - 10.1016/j.ejca.2016.10.010
M3 - Article
C2 - 27883926
AN - SCOPUS:84996619330
VL - 70
SP - 48
EP - 61
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -