Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas.
Malignant gliomas remain largely incurable despite intensive efforts to develop novel therapies. Replicating oncolytic viruses have shown great promise, among them attenuated measles viruses of the Edmonston B strain (MV-Edm). However, host immune response and the infiltrative nature of gliomas limit their efficacy. We show that human blood outgrowth endothelial cells (BOECs), readily expandable from peripheral blood, are easily infected by MV-Edm and allow replication of MV-Edm while surviving long enough after infection to serve as vehicles for MV-Edm (BOEC/MV-Edm). After intravenous and peritumoral injection, BOEC/MV-Edm deliver the viruses selectively to irradiated orthotopic U87 gliomas in mice. At the tumor, MV-Edm produced by the BOECs infect glioma cells. Subsequent spread from tumor cell to tumor cell leads to focal infection and cytopathic effects that decrease tumor size and, in the case of peritumoral injection, prolong survival of mice. Since MV-Edm within BOECs are not readily neutralized and because BOEC/MV-Edm search and destroy glioma cells, BOEC/MV-Edm constitute a promising novel approach for glioma therapy.
Wei
J
J
University Children's Hospital, Ulm, Germany.
Wahl
J
J
Nakamura
T
T
Stiller
D
D
Mertens
T
T
Debatin
K-M
KM
Beltinger
C
C
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D024201:Bystander Effect; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D042783:Endothelial Cells / Q000821:virology*; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008459:Measles virus / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D050130:Oncolytic Virotherapy / Q000379:methods*; D011897:Random Allocation; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays