Exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy.
Bifidobacteria are nonpathogenic, anaerobic domestic bacteria with health-promoting properties for the host. In our previous study, Bifidobacterium longum (B. longum) were found to be localized selectively and to proliferate within solid tumors after systemic application. Additionally, B. longum transformed by shuttle-plasmid including the cytosine deaminase (CD) gene expressed active CD, converted the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). We also demonstrated antitumor efficacy with a transformant of B. longum in rats. In this study, we found that Bifidobacterium breve (B. breve), the smallest species of human-derived bifidobacterium, expressed the exogenous transgene (CD), that CD enzymatic activity in the transformant of B. breve was much higher, and that the segregational stability of the plasmid was greater than that of B. longum. Thus, numerous transformants of B. breve were detected solely in the tumors after systemic administration. We consider the transformant of B. breve to be more beneficial in our enzyme/prodrug therapy.
Hidaka
Ayumi
A
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Hamaji
Yoshinori
Y
Sasaki
Takayuki
T
Taniguchi
Shun'ichiro
S
Fujimori
Minoru
M
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001644:Bifidobacterium / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems; D005437:Flucytosine / Q000378:metabolism* / Q000627:therapeutic use; D005472:Fluorouracil / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010957:Plasmids; D011355:Prodrugs / Q000378:metabolism* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D011355:Prodrugs; D005437:Flucytosine; D043525:Cytosine Deaminase; D005472:Fluorouracil