Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy

Replication-incompetent viral vectors are being developed for the gene ther apy of cancer. Although some of these may eventually be proven to have sign ificant localized antitumoral activity, none to date have been shown to inf ect and cause regression of established tumors following i.v. administratio n. Because cancer is a systemic disease in almost all fatal cases, the lack of i.v. efficacy is a major limitation to treatment with replication-incom petent viral vectors. ONYX-015 (dl1520) is an attenuated adenovirus that re plicates in and causes selective lysis of cancer cells. We carried out i.v. efficacy and distribution studies in nude mice with s.c. and intraparenchy mal tumor xenografts, ONYX-015 infected and replicated efficiently within t umors following i.v. administration. Viral titers in livers were relatively high 3 h after administration but decreased rapidly, becoming undetectable after 24 h, Effective antitumor doses were not associated with hepatic tox icity. Viral replication within tumors was associated with regressions in s everal tumor models. Selectively replicating viruses like ONYX-015 hold pro mise as agents to treat metastatic cancer.