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Purpose. To elucidate the influence of ionizing radiation (IR) onthe oncolytic activity of Parvovirus H-1 (H-1PV) in humanhigh-grade glioma cells. Methods. Short term cultures of humanhigh-grade gliomas were irradiated at different doses and infectedwith H-1PV. Cell viability was assessed by determining relativenumbers of surviving cells. Replication of H-1PV was measured byRT-PCR of viral RNA, fluorescence-activated cell sorter (FACS)analysis and the synthesis of infectious virus particles. Toidentify a possible mechanism for radiation induced change in theoncolytic activity of H-1PV we performed cell cycle analyses.Results. Previous irradiation rendered glioma cells fullypermissive to H-1PV infection. Irradiation 24 hours prior to H-1PVinfection led to increased cell killing most notably inradioresistant glioma cells. Intracellular levels of NS-1, themain effector of H-1PV induced cytotoxicity, were elevated afterirradiation. S-phase levels were increased one day afterirradiation improving S-phase dependent viral replication andcytotoxicity. Conclusion. This study demonstrates intactsusceptibility of previously irradiated glioma-cells for H-1PVinduced oncolysis. The combination of ionizing radiation followedby H-1PV infection increased viral cytotoxicity, especially inradioresistant gliomas. These findings support the ongoingdevelopment of a clinical trial of H-1PV in patients withrecurrent glioblastomas

Improved Killing of Human High-Grade Glioma Cells by Combining Ionizing Radiation with Oncolytic Parvovirus H-1 Infection