Cell culture models of pediatric high-grade glioma are susceptible to Parvovirus H-1 induced cytotoxicity

Oncolytic virotherapy with Parvovirus H-1 (H-1PV) represents a new therapeutic approach currently investigated in a phase I/IIa clinical trial recruiting adult patients with recurrent glioblastoma. For pediatric high-grade glioma patients there is also an urgent need of new therapeutic options. Here we analyzed, whether H-1PV is able to infect, to transduce and to selectively eliminate cell culture models of diffuse intrinsic pons glioma (DIPG) and pediatric glioblastoma in vitro.

Neurosphere cultures of DIPG (n = 4) and adherent cultures of pediatric glioblastoma (n = 4) underwent H-1PV infection either at a low or high multiplicity of infection (MOI). Productive H-1PV infection was demonstrated in all pediatric high-grade glioma cell culture models by viral protein expression, viral DNA replication and infectious virus multiplication. H-1PV infection induced significant cytostatic and cytotoxic effects as quantified by counting of viable cells and confirmed by WST-1 assay. In each DIPG neurosphere culture more than 50% of the cells were killed within 9 days after infection with H-1PV at an MOI of 10 p. f. u. per cell. In all four pediatric glioblastoma cell lines a lytic infection with H-1PV was observed and a median LD50 of 5 p. f. u. per cell was determined. Thus, in pediatric glioblastoma cell culture models the cytotoxicity of the H-1PV infection did not differ significantly from previously published data on adult glioblastoma cell lines.

In vitro H-1PV is able to infect and lyse pediatric high grade glioma cells. Future experiments will evaluate the therapeutic efficacy of H-1PV treatment in DIPG and pediatric glioblastoma-induced xenograft tumors in rodent models.