Targeting Cell Cycle Facilitates E1A-Independent Adenoviral Replication
Maximilian Ehrenfeld, Felicia Segeth, Klaus Mantwill, Corinna Brockhaus, Yuling Zhao, Christian Ploner, Andreas Kolk, Jürgen E. Gschwend, Roman Nawroth, Per Sonne Holm
Abstract
E1-deleted AdV vectors are considered replication deficient and are important tools for the study of virus biology, gene therapy, and large-scale vaccine development. However, deletion of the E1 genes does not completely abolish viral DNA replication in cancer cells. Here, we report, that the two E2F-binding sites in the adenoviral E2-early promoter contribute substantially to the so-called E1A-like activity in tumor cells. With this finding, on the one hand, the safety profile of viral vaccine vectors can be increased and, on the other hand, the oncolytic property for cancer therapy might be improved through targeted manipulation of the host cell.