p53/telomerase-dependent oncolytic adenoviruses harboring a p53-dependent feed forward loop results in reduced viral liver burden

Broad applicable vectors with highly selectivity and efficient lytic capabilities in tumors are essential for oncolytic virotherapy. Therefore, we developed selectively-replicating oncolytic viruses, which simultaneously target tumor cell-specific telomerase reexpression and p53-transcriptional deficiency, two molecular alterations which play a fundamental role in carcinogenesis and can therefore be frequently found in human tumors including hepatocellular carcinoma. The generated oncolytic viruses contained a modified Gal4-binding hTert core promoter for the viral E1A locus to achieve telomerase-dependent repli…