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

研究成果査読

149 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)881-887
ページ数7
ジャーナルNature Medicine
5
8
DOI
出版ステータスPublished - 8月 1999
外部発表はい

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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