Oncolytic Adenovirus is one of the vector systems which have potential to overcome current multiple hurdles of cancer gene therapy. Although oncolytic adenovirus selectivity target cancer cells at the step of infection may enable systemic treatment of advanced cancer, development of such vector is still an unmet goal. The mail reason of failure is extreme difficulty to genetically incorporate target cell-specific ligands to adenovirus without sacrificing potent infectivity. We recently established a method to identify a novel adenovirus targeting ligands via high-throughput screening of newly developed high-diversity adenovirus ligand library. The identified ligands were easily incorporated to adenoviruses. The oncolytic adenovirus equipped with the specific ligand showed selective infection and replication in the ligand-expressing cell lines. Furthermore, the virus achieved augmented and extremely selective antitumor effect in the xenograft of target expressing cells, compared to non-targeted virus.
In this seminar, the track record and future direction of adenovirus modification will be presented and discussed with special emphasis to the aforementioned infectivity-selective oncolytic adenovirus.