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

Oncolytic viruses have entered the field of pediatric clinical research with the first early phase clinical trial recently published. Based on promising pre-clinical studies, the oncolytic parvovirus H-1 (H-1PV) has been applied to adult glioblastoma patients in a phase I/IIa clinical trial, indicating clinical safety of intracranial and intravenous virus application. Here, we characterized the cytotoxic effects induced by the oncolytic parvovirus H-1 in conventional pediatric high-grade glioma (HGG) cell culture models and neurosphere cultures derived thereof.

Adherent cultures derived from diffuse intrinsic pontine glioma (n = 3) and from pediatric glioblastoma (n = 4) were tested for efficacy of viral transduction, viral replication, and virus-induced cytotoxicity. H-1PV is able to enter and get expressed in all adherent pediatric high grade glioma cell lines. H-1PV is able to infect pediatric as well as adult high-grade glioma neurosphere cultures analyzed (n = 6), irrespective of the histological subtype or age of the patient. In all susceptible neurosphere cultures the cytotoxic effects induced by H-1PV infection were observed at LD50 doses of input virus between 1 and 10 p. f. u. per cell. More-over, H-1PV infection suppressed tumorigenicity of HGG neurospheres in SCID mice. Thus, H-1PV deserves to proceed to the next steps of pre-clinical research in order to prepare a clinical trial in pediatric high-grade glioma patients.