title: Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses.
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.
authors.affiliation: Molecular Neuro-Oncology Laboratories, Neurosurgery Service, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Ichikawa
authors.forename: H
authors.initials: H
authors.lastname: Wakimoto
authors.forename: J S
authors.initials: JS
authors.lastname: Silver
authors.forename: T S
authors.initials: TS
authors.lastname: Deisboeck
authors.forename: D
authors.initials: D
authors.lastname: Finkelstein
authors.forename: G R
authors.initials: GR
authors.lastname: Harsh
authors.forename: D N
authors.initials: DN
authors.lastname: Louis
authors.forename: R T
authors.initials: RT
authors.lastname: Bartus
authors.forename: F H
authors.initials: FH
authors.lastname: Hochberg
authors.forename: E A
authors.initials: EA
authors.lastname: Chiocca
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects; D001932:Brain Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy / Q000821:virology; D003165:Complement System Proteins / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D005910:Glioma / Q000276:immunology* / Q000401:mortality / Q000628:therapy / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007075:Immunoglobulin M / Q000097:blood; D007165:Immunosuppression Therapy; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D015996:Survival Rate; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014780:Viruses / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000914:Antibodies, Viral; D007075:Immunoglobulin M; D003520:Cyclophosphamide; D003165:Complement System Proteins