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Controlling brain tumor growth by intraventricular administration of an AAV vector encoding IFN-β

Cancer Gene Therapy volume 16, pages 664–671 (2009)Cite this article

Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of all primary brain tumors, with an overall median survival <1 year after diagnosis. Despite introduction of multimodal treatment approaches, the prognosis has not improved significantly over the past 50 years. In this study we investigated the effect of intracerebroventricular (ICV) injection of an adeno-associated virus (AAV) vector encoding human interferon-β (AAV-hIFN-β) on glioblastoma growth. Recently, we found that peritumoral parenchymal transduction with an AAV-hIFN-β was exceptionally efficient in eradicating GBM brain tumors. However, the extensive infiltration and migration displayed by glioblastoma cells in patients may leave a significant number of tumor cells outside a local therapeutic zone created by intraparenchymal delivery of AAV vectors. Here we show that pretreatment of mice by ICV infusion of an AAV-IFN-β completely prevents tumor growth in an orthotopic model of GBM. Furthermore, ICV infusion of AAV-IFN-β into mice bearing preestablished U87 intracranial tumors improved their survival compared to mice infused through the same route with a control AAV vector. These data suggest that ICV injection of AAV vectors encoding antitumor proteins is a promising approach deserving further consideration for the treatment of GBM.

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Acknowledgements

This work was supported by a Young Investigator Award from the Alliance for Cancer Gene Therapy (MSE), and NIH 5 T32 CA073479-09 (CM). We acknowledge the Massachusetts General Hospital Neuroscience Center Microscopy and Image Analysis Core (NIH grant P30NS045776) for the use of the Nikon scanner, and we thank Dr Ralph Weissleder, Director of the Center for Molecular Imaging Research, for the use of the bioluminescence imager.

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Author notes

  1. D H Meijer and C A Maguire: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA

    D H Meijer, C A Maguire, S G LeRoy & M Sena-Esteves

  2. Neuroscience Program, Harvard Medical School, Boston, MA, USA

    D H Meijer, C A Maguire, S G LeRoy & M Sena-Esteves

  3. Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

    D H Meijer

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  1. D H Meijer
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  2. C A Maguire
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  4. M Sena-Esteves
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Correspondence to M Sena-Esteves.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website (http://www.nature.com/cgt)

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Meijer, D., Maguire, C., LeRoy, S. et al. Controlling brain tumor growth by intraventricular administration of an AAV vector encoding IFN-β. Cancer Gene Ther 16, 664–671 (2009). https://doi.org/10.1038/cgt.2009.8

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