In Combinatorial treatment approaches Parvovirus H-1 increases antineoplastIc efficacy in High grade glioma and neuroblastoma models

Parvovirus H-1 (H-1PV) is an oncolytic wild type virus with proven clinical safety in adult glioblastoma patients. As a preparatory step towards a clinical application of H-1PV in pediatric neurooncology combinatorial treatment approaches have been pre-clinically evaluated for pediatric high-grade glioma (HGG) and high risk neuroblastoma (NB). HGG (n = 7) and high-risk NB (n = 10) cell lines were tested for the efficacy of viral transduction, viral replication, virus-induced cytotoxicity and response to conventional cytostatic drugs. H-1PV successfully infected all NB and HGG cell lines irrespective of cytostatic treatment and induced cell lysis LD50 doses of input virus between 0.1 and 50 p. f. u. per cell. In HGG and NB cell culture models combinatorial treatment approaches were identified, in which simultaneous administration of cytostatic drugs and H-1PV increased treatment efficacy in an additive or even synergistic way. A significant increase of the antineoplastic efficacy was observed in vivo when combining intratumoral injection of H-1PV with intra-peritoneal doxorubicine treatment in a subcutaneous, MYCN amplified NB xenograft model. In animals bearing subcutaneous glioblastoma xenografts a combined treatment with intratumoral H-1PV and oral TMZ significantly prolonged survival, as compared to the respective monotherapies. The present data show the potential of oncolytic parvovirotherapy to be integrated into established treatment schedules for pediatric neurooncology.