Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer.
Tumor-targeting bacteria have been studied in terms of their ability to visualize the infection pathway (through imaging probes) or to carry therapeutic molecules to tumors. To integrate these monitoring and therapeutic functions, we engineered attenuated Salmonella typhimurium defective in guanosine 5'-diphosphate-3'-diphosphate synthesis to carry cytotoxic proteins (cytolysin A) and express reporter genes. We successfully visualized the therapeutic process with these engineered bacteria in mice and found that they often mediated complete tumor (CT-26) eradication on cytotoxic gene induction. Furthermore, treatment with the engineered bacteria markedly suppressed metastatic tumor growth.
Nguyen
Vu H
VH
Department of Nuclear Medicine, Chonnam National University Medical School, Dong-gu, Gwangju, Republic of Korea.
Kim
Hyung-Seok
HS
Ha
Jung-Min
JM
Hong
Yeongjin
Y
Choy
Hyon E
HE
Min
Jung-Joon
JJ
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D005818:Genetic Engineering / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000628:therapy*; D054353:Perforin / Q000235:genetics* / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D012486:Salmonella typhimurium / Q000235:genetics*; D051025:bcl-Associated Death Protein / Q000235:genetics
D051025:bcl-Associated Death Protein; D054353:Perforin