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Bioeng Bugs. 2010 Nov-Dec;1(6):429-33. doi: 10.4161/bbug.1.6.12943.

Therapeutic implications of the enhanced short and long-term cytotoxicity of radiation treatment followed by oncolytic parvovirus H-1 infection in high-grade glioma cells.

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  • 1Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany. k.geletneky@dkfz.de

Abstract

The prognosis of malignant brain tumors remains extremely bad in spite of moderate improvements of conventional treatments. A promising alternative approach is the use of oncolytic viruses. Strategies to improve viral toxicity include the combination of oncolytic viruses with standard therapies. Parvovirus H-1 (H-1PV) is an oncolytic virus with proven toxicity in glioma cells. Recently it has been demonstrated that the combination of ionizing radiation (IR) with H-1PV showed promising results. Previously irradiated glioma cells remained fully permissive for H-1PV induced cytotoxicity supporting the use of H-1PV for recurrent gliomas, which typically arise from irradiated cell clones. When glioma cells were infected with H-1PV shortly (24 h) after IR, cell killing improved and only the combination of both treatments lead to complete long-term tumor cell killing. The latter finding raises the question whether IR in combination with H-1PV exerts an additional therapeutic effect on highly resistant glioma stem cells. A likely translation into current clinical treatment protocols is to use stereotactic radiation of non-resectable recurrent gliomas followed by intratumoral injection of H-1PV to harvest the synergistic effects of combination treatment.

© 2010 Landes Bioscience

KEYWORDS:

combination therapy; malignant glioma; oncolytic virus; parvovirus H-1; radiation therapy; stem cells

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