Overexpression of Adenovirus-Encoded Transgenes from the Cytomegalovirus Immediate Early Promoter in Irradiated Tumor Cells

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Abstract
Efficient expression of therapeutic genes in irradiated tumor cells would facilitate the conversion of a malignant tumor nodule into a cancer vaccine in situ. We reported previously that transgene expression from an adenoviral vector could be markedly enhanced by treating transduced tumor cells with butyrate. In this study, we demonstrated that a similar butyrate effect could be achieved in irradiated tumor cells. In addition, irradiating cells at doses of 2–40 Gy prior to transduction could also amplify recombinant adenoviral transgene products in a cell-type-specific manner. This suggests that adenovirus-mediated gene therapy, radiation therapy, and butyrate-mediated cancer therapy may potentially be formulated into one synergistic protocol for cancer treatment. This study demonstrates that transgenes from recombinant adenoviral vectors can be efficiently expressed in irradiated tumor cells, and the level of transgene expression can be further augmented by treating irradiated/transduced tumor cells with butyrate. Results suggest that adenovirus-mediated gene therapy, radiation therapy, and butyrate-mediated cancer therapy may be formulated into a synergistic protocol for eliciting anticancer effects that are potentially more protective than those achievable by a single remedy.