Genetically engineeredbifidobacterium as a drug delivery system for systemic therapy of metastatic breast cancer patients

摘要

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 asBifidobacterium orClostridium selectively localizes to and proliferates in solid tumors after systemic application. Another approach uses attenuatedSalmonella strains that need tumor-specific nutrients to selectively proliferate and is a potential gene delivery system. We constructed a plasmid, pBLESl00-S-eCD, which included the cytosine deaminase gene. TransfectedBifidobacterium longum produced cytosine deaminase in the hypoxic tumor. Enzyme/pro-drug therapy was confirmed to be effective for systemic administration.