Open AccessTargeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas
Author(s) -
Jiwu Wei,
Joachim Wahl,
Takafumi Nakamura,
Detlef Stiller,
Thomas Mertens,
KlausMichael Debatin,
Christian Beltinger
Publication year - 2007
Publication title -
gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.332
H-Index - 159
eISSN - 1476-5462
pISSN - 0969-7128
DOI - 10.1038/sj.gt.3303027
Subject(s) - oncolytic virus , glioma , measles virus , cancer research , measles , medicine , polylysine , virology , immunology , biology , virus , vaccination , biochemistry
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.