Genetically engineered bifidobacterium as a drug delivery system for systemic therapy of metastatic breast cancer patients.
A fundamental obstacle in systemic therapy for metastatic breast cancer patients is specific targeting of therapy directly to a solid tumor. Hypoxic or necrotic regions are characteristic of solid tumors in many murine and human tumors, including the majority of primary tumors of the breast. A strain of anaerobic bacteria such as Bifidobacterium or Clostridium selectively localizes to and proliferates in solid tumors after systemic application. Another approach uses attenuated Salmonella strains that need tumor-specific nutrients to selectively proliferate and is a potential gene delivery system. We constructed a plasmid, pBLES100-S-eCD, which included the cytosine deaminase gene. Transfected Bifidobacterium longum produced cytosine deaminase in the hypoxic tumor. Enzyme/pro-drug therapy was confirmed to be effective for systemic administration.
Fujimori
Minoru
M
Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan. minoru1@hsp.md.shinshu-u.ac.jp
D000818:Animals; D001644:Bifidobacterium / Q000201:enzymology / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000628:therapy*; D043525:Cytosine Deaminase / Q000235:genetics* / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D010957:Plasmids; D014162:Transfection
D043525:Cytosine Deaminase