Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses

Keiro Ikeda, Tomotsugu Ichikawa, Hiroaki Wakimoto, Jonathan S. Silver, Thomas S. Deisboeck, Dianne Finkelstein, Griffith R. Harsh IV, David N. Louis, Raymond T. Bartus, Fred H. Hochberg, E. Antonio Chiocca

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

The occurrence of multiple tumors in an organ heralds a rapidly fatal course. Although intravascular administration may deliver oncolytic viruses/vectors to each of these tumors, its efficiency is impeded by an antiviral activity present in complement-depleted plasma of rodents and humans. Here, this activity was shown to interact with complement in a calcium-dependent fashion, and antibody neutralization studies indicated preimmune IgM has a contributing role. Short-term exposure to cyclophosphamide (CPA) partially suppressed this activity in rodents and humans. At longer time points, cyclophosphamide also abrogated neutralizing antibody responses. Cyclophosphamide treatment of rats with large single or multiple intracerebral tumors substantially increased viral survival and propagation, leading to neoplastic regression.

Original languageEnglish
Pages (from-to)881-887
Number of pages7
JournalNature Medicine
Volume5
Issue number8
DOIs
Publication statusPublished - Aug 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ikeda, K., Ichikawa, T., Wakimoto, H., Silver, J. S., Deisboeck, T. S., Finkelstein, D., Harsh IV, G. R., Louis, D. N., Bartus, R. T., Hochberg, F. H., & Antonio Chiocca, E. (1999). Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses. Nature Medicine, 5(8), 881-887. https://doi.org/10.1038/11320