Controlling Adenoviral Replication to Induce Oncolytic Efficacy

ABSTRACT

Over the last decade, cancer therapy has found itself challenged by the growing field of oncolytic virotherapy. Many different viruses are currently under study, investigating their potential to induce antitumor effects through repeated cycles of viral infection and cell lysis. It was, however, genetically-engineered replication-selective adenoviruses that were the first to enter clinical trials with cancer patients. The difficulties involved in combining selectivity and elevated potency in a single oncolytic adenovirus have led investigators to design and test many different approaches. Different strategies, based on the control of viral replication, are presented in the current review. We discuss how the growing knowledge of cell and tumour biology, with the advances made in adenoviral virology, has inspired the fine-tuning of genetically-engineered adenoviruses. Special emphasis is placed on the fundamentals behind the use of certain specific genetic elements, introduced into the viral genome to control viral gene expression and on describing the most important viral gene mutations.

Keywords:

Adenovirus, oncolysis, cancer virotherapy, transcriptional targeting, post-transcriptional targeting, cancer gene therapy, insulators, tumor microenvironment.