Re-engineering adenovirus regulatory pathways to enhance oncolytic specificity and efficacy

Replicating adenoviruses may prove to be effective anticancer agents if the y can be engineered to selectively destroy tumor cells. We have constructed a virus (01/PEME) containing a novel regulatory circuit in which p53-depen dent expression of an antagonist of the E2F transcription factor inhibits v iral replication in normal cells. In tumor cells, however, the combination of p53 pathway defects and deregulated E2F allows replication of 01/PEME at near wild-type levels. The re-engineered virus also showed significantly e nhanced efficacy compared with extensively studied E1b-deleted viruses such as d/1520 in human xenograft tumor models.