Oncolytic adenovirus research and applications

Abstract

Cancer treatments have improved steadily, but still only few metastatic solid tumors can be cured. Apoptosis-resistant clones frequently develop following standard treatments. Resistance factors are shared between different treatment regimens and, therefore, loss of response can occur rapidly, despite changing the drug, and there is a tendency for crossresistance between modalities. Therefore, new agents with novel mechanisms of action are desperately needed. Oncolytic adenoviruses, featuring cancer-selective cell lysis and spread, constitute an interesting drug platform aimed towards the goals of tumor specificity, and have been engineered in a variety of ways to improve their selectivity and efficacy. They allow rational drug development by the genetic incorporation of targeting mechanisms that can exert their function at different stages of the viral replication cycle. Owing to their immunogenicity, adenoviruses are particularly attractive for immunostimulatory purposes.