An oncolytic adenovirus encoding decorin and GM-CSF inhibits tumor growth in a colorectal tumor model by targeting pro-tumorigenic signals and via immune-activation

In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients’ tumors, while, there were increased Met and VEGFA levels. To develop a novel therapy for CRC, we have created rAd.DCN.GM, an oncolytic adenovirus encoding decorin and granulocyte macrophage colony stimulating factor (GM-CSF). Several therapeutic strategies expressing GM-CSF have been employed in the clinical trials for treating metastatic colorectal cancer. In this study, infection of CRC cells with rAd.DCN.GM expressed decorin and GM-CSF, and produced cytotoxicity. In murine CT26 xenografts, rAd.DCN.GM a...