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Authors: Karsten Geletneky, Andreas D. Hartkopf, Robert Krempien, Jean Rommelaere and Joerg R. Schlehofer

Karsten Geletneky

Corresponding author: k.geletneky@dkfz.de
Department of Neurosurgery, University of Heidelberg 69120 Heidelberg, Germany; German Cancer Research Center, Department of Applied Tumor Virology 69120 Heidelberg, Germany

Andreas D. Hartkopf

Department of Gynaecology, University of Tuebingen 72076Tuebingen, Germany

Robert Krempien

Department of Radiation Oncology, HELIOS-Klinikum Berlin 13125 Berlin, Germany

Jean Rommelaere

German Cancer Research Center, Department of Applied Tumor Virology 69120 Heidelberg, Germany

Joerg R. Schlehofer

German Cancer Research Center, Department of Applied Tumor Virology 69120 Heidelberg, Germany

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.