Combinatory use of replication-competent adenoviruses and chemotherapeutic agents produces anti-tumor effects on human esophageal carcinoma cells

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We examined a novel therapeutic strategy for intractable cancer in particular esophageal carcinoma. We replaced a transcriptional regulatory region of the E1 region-encoded genes in adenoviruses (Ad) with a 5' region of a gene that was highly expressed in human tumors but not in normal tissues such as midkine, survivin and cyclooxygenase-2. We also changed the fiber region of conventional type 5 Ad, which played a key role in infecting target cells, with a type 35-derived fiber region. The modification increased the viral infectivity since an expression level of the CAR molecules, which were a cellular receptor of type 5 Ad, were often down-regulated in human tumors. In contract, the expression of CD46 molecules, which are the major receptor of type 35 Ad, is rather up-regulated in human tumors. The fiber replacement greatly enhanced Ad infectivity in CAR-low tumors and subsequently enhanced the Ad-mediated cytotoxicity, and produced combinatory effects with anti-cancer agents.