title: 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.
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.
authors.affiliation: Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany. k.geletneky@dkfz.de
authors.forename: Karsten
authors.initials: K
authors.lastname: Geletneky
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Hartkopf
authors.forename: Robert
authors.initials: R
authors.lastname: Krempien
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.forename: Joerg R
authors.initials: JR
authors.lastname: Schlehofer
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology*; D002470:Cell Survival / Q000528:radiation effects; D003131:Combined Modality Therapy; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology*; D052661:H-1 parvovirus / Q000502:physiology*; D006801:Humans; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000528:radiation effects / Q000821:virology