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Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity

Gene Therapy volume 8, pages 746–759 (2001)Cite this article

Abstract

Although genetically engineered adenoviruses hold promise for the treatment of cancer, clinical trial reports have utilized intratumoral injection to date. To determine the feasibility of intravenous delivery of ONYX-015, an E1B-55kD gene-deleted replication selective adenovirus with demonstrated clinical safety and antitumoral activity following intratumoral injection, we performed a clinical trial in patients with metastatic solid tumors. ONYX-015 was infused intravenously at escalating doses of 2 × 1010 to 2 × 1013 particles via weekly infusion within 21-day cycles in 10 patients with advanced carcinoma metastatic to the lung. No dose-limiting toxicity was identified. Mild to moderate fever, rigors and a dose-dependent transient transaminitis were the most common adverse events. Neutralizing antibody titers significantly increased within 3 weeks in all patients. IL-6, γ-IFN, TNF-α and IL-10 increased within 24 h following treatment. Evidence of viral replication was detectable in three of four patients receiving ONYX-015 at doses ⩾2 × 1012 particles and intratumoral replication was confirmed in one patient. In conclusion, intravenous infusion of ONYX-015 was well tolerated at doses up to 2 × 1013 particles and infection of metastatic pulmonary sites with subsequent intratumoral viral replication was seen. The intravenous administration of genetically altered adenovirus is a feasible approach.

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Acknowledgements

We wish to thank Ana Petrovich for manuscript preparation, Sherry Toney for extensive time and effort in coordinating study samples and results as well as editorial proofing of the manuscript, and George Smith and Carrie LeDuc from Althea for providing extensive assistance in determining ONYX-015 DNA analysis.

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Authors and Affiliations

  1. US Oncology, Dallas, TX, USA

    J Nemunaitis, C Cunningham, A Buchanan, A Blackburn, G Edelman & P Maples

  2. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA

    J Nemunaitis, C Cunningham, G Netto & A Tong

  3. Onyx Pharmaceuticals, Richmond, CA, USA

    B Randlev

  4. Warner-Lambert Corporation, Ann Arbor, MI, USA

    S Olson

  5. Imperial Cancer Research Fund and Imperial College School of Medicine, London, UK

    D Kirn

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  1. J Nemunaitis
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Nemunaitis, J., Cunningham, C., Buchanan, A. et al. Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity. Gene Ther 8, 746–759 (2001). https://doi.org/10.1038/sj.gt.3301424

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