All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

Abstract

Abstract. Reoviridae are non-human pathogenic viruses. The family of reoviridae consists of 4 different subtypes. Many studies have proven that the Dearing subtype 3 has oncolytic potential. This potential is related to the RAS protein expression in tumour cells. The aim of this study, was to investigate whether all reovirus subtypes have oncolytic potential and whether there are differences in their efficacy, in particular for high-grade glioma. To evaluate the oncolytic potential, we performed an in vitro head-to-head study for all reovirus subtypes in 5 primary cell cultures of high-grade gliomas. The oncolytic activity was determined using end-point titration with observation of the cytopathogenic effect. For measurement of RAS activity, we performed an immunofluorescent detection stain on all cell cultures. For quantification of the virus, an RT-PCR measurement for all subtypes was performed. All reovirus subtypes showed oncolytic activity in the observed glioma biopsies. These observations correlated with RAS overexpression in the observed cells. All glioma biopsies overexpressed the RAS protein. The quantitative oncolytic potential differed in relation to the single observed cell culture and in relation to the chosen reovirus subtype. To our knowledge, this is the first study showing oncolytic activity for all reovirus subtypes. We show the relationship and correlation between RAS protein overexpression and vulnerability of cells to reovirus. Efficacy of the different subtypes is interindividually different and cannot be forecast.

Comparative proteomic analyses of two reovirus T3D subtypes and comparison to T1L identifies multiple novel proteins in key cellular pathogenic pathways

“…Reovirus type 3 Dearing, isolate Cashdollar (T3D C ) is currently being used in clinical studies and is mainly studied for its oncolytic properties . Recently, all of the reovirus subtypes have been shown to have oncolytic potential . Reovirus strains differ in both replication and pathogenic characteristics.…”

Oncolytic Virus Therapy for Glioblastoma Multiforme

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Exploring the antitumor effect of virus in malignant glioma

“…While intracranial reovirus administration was neurotoxic in severely immunodeficient animals (77), it was nontoxic in immunocompetent rodents and nonhuman primates (78). Recently, all four serotypes of reovirus have been shown to have oncolytic activity in glioma cell lines, as well as in GSCs (79, 80). …”