Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I/IIa Glioblastoma Trial

Mol Ther. 2017 Dec 6;25(12):2620-2634. doi: 10.1016/j.ymthe.2017.08.016. Epub 2017 Aug 24.


Oncolytic virotherapy may be a means of improving the dismal prognosis of malignant brain tumors. The rat H-1 parvovirus (H-1PV) suppresses tumors in preclinical glioma models, through both direct oncolysis and stimulation of anticancer immune responses. This was the basis of ParvOryx01, the first phase I/IIa clinical trial of an oncolytic parvovirus in recurrent glioblastoma patients. H-1PV (escalating dose) was administered via intratumoral or intravenous injection. Tumors were resected 9 days after treatment, and virus was re-administered around the resection cavity. Primary endpoints were safety and tolerability, virus distribution, and maximum tolerated dose (MTD). Progression-free and overall survival and levels of viral and immunological markers in the tumor and peripheral blood were also investigated. H-1PV treatment was safe and well tolerated, and no MTD was reached. The virus could cross the blood-brain/tumor barrier and spread widely through the tumor. It showed favorable pharmacokinetics, induced antibody formation in a dose-dependent manner, and triggered specific T cell responses. Markers of virus replication, microglia/macrophage activation, and cytotoxic T cell infiltration were detected in infected tumors, suggesting that H-1PV may trigger an immunogenic stimulus. Median survival was extended in comparison with recent meta-analyses. Altogether, ParvOryx01 results provide an impetus for further H-1PV clinical development.

Keywords: clinical trial; glioblastoma; oncolytic parvovirus; tumor microenvironment.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Female
  • Gene Expression
  • Genetic Therapy* / adverse effects
  • Genetic Therapy* / methods
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • H-1 parvovirus / genetics*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Oncolytic Virotherapy* / adverse effects
  • Oncolytic Virotherapy* / methods
  • Oncolytic Viruses / genetics*
  • Radiotherapy
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Transgenes
  • Treatment Outcome