Nature Medicine
5, 881 - 887 (1999)
doi:10.1038/11320
Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responsesKeiro Ikeda1, Tomotsugu Ichikawa1, Hiroaki Wakimoto1, Jonathan S. Silver2, Thomas S. Deisboeck1, Dianne Finkelstein3, Griffith R. Harsh IV1, David N. Louis1, 2, Raymond T. Bartus4, Fred H. Hochberg5
& E. Antonio Chiocca11
Molecular Neuro-Oncology Laboratories, Neurosurgery Service, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
2
Molecular Neuro-Oncology Laboratories, Neuropathology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
3
MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
4
Alkermes, Cambridge, Massachusetts 02111, USA
5
Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Correspondence should be addressed to E. Antonio Chiocca Chiocca@helix.mgh.harvard.eduThe 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.
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