Abstract
Abstract : The overall goal was to develop infectivity enhanced fit-1 promoter-based conditionally replicative adenovirus (CRAd) and investigates effects of CRAd virotherapy on breast cancer cells in vitro. We have developed a CRAd using the fit-i promoter element for specific E1A gene expression (CRAdflt), RGD-4C-containing peptide in the HI loop of the Ad fiber knob region (CRAdRGflt) and encoding the melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) gene (CRAdRGflt-mda-7) and a ROD- 4C modification in the fiber knob domain. In vitro experimental data provided evidence of relatively high levels of fit-i promoter activity in human and mouse blood vessel endothelial cells and in certain human breast cancer cell lines. The comparative levels of CRAd replication in cancer cells correlated with fit-i promoter activity. RGD-4C modification in the fiber-knob region increased cytotoxicity of CRAdRGflt in comparison with CRAdflt. The breast cancer cells demonstrated different levels of sensitivity to CRAdRGflt-mda-7 infection. The induction of apoptosis in cancer cells after CRAdRGflt-mda-7 infection was demonstrated.
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