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

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

Author information

1
Department of Neurosurgery, University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
2
Coordination Centre for Clinical Trials, University Hospital, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany.
3
Department of Tumor Virology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
4
Department of Neuropathology, University Hospital, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
5
Department of Neuroradiology, University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
6
University Hospital Pharmacy, Im Neuenheimer Feld 670, 69120 Heidelberg, Germany.
7
Department of Neuropathology, University Medical Center, Georg August University, 37099 Göttingen, Germany.
8
Eurofins BioPharma Product Testing, Behringstraße 6/8, 82152 Planegg, Germany.
9
Laboratory Prof. Dr. Gisela Enders & Colleagues, MVZ and Institute of Virology, Infectious Diseases and Epidemiology e.V., Stuttgart, Germany.
10
ProImmune, The Magdalen Centre, Oxford Science Park, Oxford OX4 4GA, UK.
11
IASON Consulting, Mühlenstraße 26A, 52382 Niederzier, Germany.
12
Department of Transplantation Immunology, Institute of Immunology, University Hospital, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
13
Oryx GmbH & Co. KG, Marktplatz 1, 85598 Baldham, Germany.
14
Department of Tumor Virology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. Electronic address: j.rommelaere@dkfz.de.

Abstract

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

PMID:
28967558
PMCID:
PMC5768665
DOI:
10.1016/j.ymthe.2017.08.016
[Indexed for MEDLINE]
Free PMC Article

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