Strategies for Improving the Systemic Delivery of Oncolytic Adenoviruses and Plasmids: Potential Application of Non-Viral Carriers
Pp. 190-225 (36)
Mireia Agirre, Jon Zarate, Gustavo Puras, Luis A. Rojas, Ramon Alemany and José L. Pedraz
Virotherapy is the use of oncolytic or tumor-selective viruses to treat cancer.
The replication of the virus inside a tumor can debulk the tumor mass and
simultaneously, revert the immune suppressor environment that causes the immune
escape of tumor cells. This therapeutic approach was discovered ten years ago but it has
been renewed in the last decade with designed viruses. Adenovirus (Ad) is a nonenveloped
DNA virus that infects broadly tumor cells and it has been frequently used in
cancer gene therapy and virotherapy. A very high level of tumor-specific replication has
been obtained with adenoviruses by replacing early viral gene promoters with tumorselective
promoters. However, the complex Ad capsid interactions with blood proteins
and cells and, also with liver and spleen macrophages result in rapid blood clearance
and the prevention of systemic tumor targeting. To settle these problems, a new field is
emerging where an oncolytic Ad genome is complexed to non-viral vectors to target
Oncolytic viruses, non-viral vectors, oncolytic adenoviral genome,
modified adenoviruses, tumor targeting.
Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, 01006, Vitoria-Gasteiz, Spain.