Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy.
Replication-incompetent viral vectors are being developed for the gene therapy of cancer. Although some of these may eventually be proven to have significant localized antitumoral activity, none to date have been shown to infect and cause regression of established tumors following i.v. administration. 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-incompetent viral vectors. ONYX-015 (d11520) is an attenuated adenovirus that replicates in and causes selective lysis of cancer cells. We carried out i.v. efficacy and distribution studies in nude mice with s.c. and intraparenchymal tumor xenografts. ONYX-015 infected and replicated efficiently within tumors 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 toxicity. Viral replication within tumors was associated with regressions in several tumor models. Selectively replicating viruses like ONYX-015 hold promise as agents to treat metastatic cancer.
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ONYX Pharmaceuticals, Richmond, California 94806, USA.
Williams
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Xue
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Propst
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Kirn
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D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000032:analysis; D003673:Defective Viruses / Q000502:physiology*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D019073:HT29 Cells / Q000821:virology; D006801:Humans; D017403:In Situ Hybridization; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy* / Q000821:virology; D013997:Time Factors; D014183:Transplantation, Heterologous; D014779:Virus Replication
D004279:DNA, Viral