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.

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