Intravenous and isolated limb perfusion delivery of wild type and a tumor-selective replicating mutant vaccinia virus in nonhuman primates

Arpana M. Naik, Sricharan Chalikonda, J. Andrea McCart, Hui Xu, Z. Sheng Guo, Gregory Langham, Donald Gardner, Simone Mocellin, Anna E. Lokshin, Bernard Moss, H. Richard Alexander, David L. Bartlett

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    Abstract

    In this study we examine the safety, feasibility, and biodistribution of a tumor-selective mutant vaccinia (vvDD) and wild-type WR (vF13) vaccinia after delivery via intradermal or intravenous infection or isolated limb perfusion (ILP) in rhesus macaques. By intradermal inoculation, 106 PFU of vvDD caused a minimal skin reaction whereas vF13 caused marked erythema and necrosis with a peak indurated area of 108 cm2. By intravenous delivery, vvDD caused no clinical symptoms of viremia and no viral recovery from tissues, serum, saliva, urine, or feces. In contrast, vF13 caused symptoms of lethargy, anorexia, fever, and signs of viremia. Delivery of vF13 via ILP resulted in numerous cutaneous pox lesions localized solely to the perfused limb with high viral recovery in the perfused skin and muscle. ILP with vvDD resulted in no visible pox lesions and no clinical signs or symptoms of viremia. No long-term toxicity was identified after ILP with 109 PFU of vvDD, and no virus was recovered from any tissue, serum, saliva, urine, or fecal sample. These results suggest that vvDD appears to be safe in primates, and thus vvDD should be further investigated for clinical trial in human cancer patients.

    Original languageEnglish (US)
    Pages (from-to)31-45
    Number of pages15
    JournalHuman Gene Therapy
    Volume17
    Issue number1
    DOIs
    StatePublished - Jan 1 2006

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    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics

    Cite this

    Naik, A. M., Chalikonda, S., McCart, J. A., Xu, H., Guo, Z. S., Langham, G., Gardner, D., Mocellin, S., Lokshin, A. E., Moss, B., Alexander, H. R., & Bartlett, D. L. (2006). Intravenous and isolated limb perfusion delivery of wild type and a tumor-selective replicating mutant vaccinia virus in nonhuman primates. Human Gene Therapy, 17(1), 31-45. https://doi.org/10.1089/hum.2006.17.31