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Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas

Gene Therapy volume 14, pages 1573–1586 (2007)Cite this article

Abstract

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.

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Acknowledgements

We thank L Liu for statistical analysis. This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (to CB).

Author information

Author notes

  1. J Wei

    Present address: 6Current address: Division of Clinical Pharmacology, Section of Gastroenterology, Medizinische Klinik Innenstadt, University of Munich, Ziemssenstr. 1, 80336 Munich, Germany.,

  2. T Nakamura

    Present address: 7Current address: Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 3–1–1 Maidashi, Fukuoka 812-8582, Japan.,

  3. J Wei and J Wahl: These authors have contributed equally to this work.

Authors and Affiliations

  1. University Children's Hospital, Ulm, Germany

    J Wei, J Wahl, K-M Debatin & C Beltinger

  2. Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN, USA

    T Nakamura

  3. Boehringer Ingelheim Pharma, Biberach an der Ri, ß, Germany

    D Stiller

  4. Department of Virology, University Hospital, Ulm, Germany

    T Mertens

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  1. J Wei
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  2. J Wahl
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  3. T Nakamura
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  6. K-M Debatin
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  7. C Beltinger
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Corresponding author

Correspondence to C Beltinger.

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Wei, J., Wahl, J., Nakamura, T. et al. Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas. Gene Ther 14, 1573–1586 (2007). https://doi.org/10.1038/sj.gt.3303027

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  • DOI: https://doi.org/10.1038/sj.gt.3303027

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