Conditionally Replicative Adenoviruses-Clinical Trials

Oncolytic viruses are emerging as a promising alternative for cancer therapy. Among these biologic agents, adenoviruses have been extensively tested as vectors to transfer exogenous genes to cancer cells. Sophisticated modifications of the adenovirus genome to improve infectivity and selectivity have made possible the production of replicating adenoviruses intended to directly destroy tumors by cell lysis. In this chapter, we discuss the origins of virotherapy and early trials with wild-type adenoviruses and other viruses, and the concept underlying the development of replication-deficient adenoviral vectors, with special emphasis on Ad-p53. We then review clinical findings for dl1520 and H101 oncolytic adenoviruses and, finally, the concepts of Delta-24, Delta-24-RGD, and ICOVIR, emphasizing clinical applications. A dramatic increment in clinical trials over the next 5 years will lead to the approval of oncolytic viruses for conventional cancer treatment within the next decade.