Klin Padiatr 2015; 227 - A10
DOI: 10.1055/s-0035-1564676

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

R Josupeit 1, S Bender 1, B Leuchs 1, C Herold-Mende 2, JR Schlehofer 1, O Witt 3, 4, J Rommelaere 1, J Jeannine Lacroix 1, 4
  • 1Division of Tumor Virology, Program “Infection and Cancer”, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 2Division of Experimental Neurosurgery, Department of Neurosurgery, University Hospital, Heidelberg, Germany
  • 3Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 4Department of Pediatric Hematology, Oncology and Immunology, University Hospital Heidelberg, Germany

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.