Replication-selective adenoviruses as oncolytic agents

Adenovirus biology and cancer biology have progressed in a complementary fashion. For example, proteins encoded at the virus’ E1 region were found to bind to the tumor suppressor proteins p53 and pRB, and these interactions played an important role in characterizing the role of these tumor suppressors in virus-dependent and -independent transformation (1, 2). Perhaps, then, it is a natural extension of this history that human adenoviruses are now being developed as anticancer agents. Ironically, although advances in genetic engineering have permitted the development of replication-disabled adenoviruses as simple delivery vehicles for therapeutic genes (3–5), replication-competent wildtype strains were actually the first to be administered safely to patients (6). Now, nearly a half-century later, replication-competent adenoviruses are once again being studied as therapeutic agents (7–9). However, genetic engineering has now been used with the goal of maximizing tumor-selective replication.