Oncolytic H-1 parvovirus shows safety and signs of immunogenic activity in a first phase I/IIa glioblastoma trial
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 p...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 August 2017
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| In: |
Molecular therapy
Year: 2017, Volume: 25, Issue: 12, Pages: 2620-2634 |
| ISSN: | 1525-0024 |
| DOI: | 10.1016/j.ymthe.2017.08.016 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.ymthe.2017.08.016 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1525001617303787 
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| Author Notes: | Karsten Geletneky, Jacek Hajda, Assia L. Angelova, Barbara Leuchs, David Capper, Andreas J. Bartsch, Jan-Oliver Neumann, Tilman Schöning, Johannes Hüsing, Birgit Beelte, Irina Kiprianova, Mandy Roscher, Rauf Bhat, Andreas von Deimling, Wolfgang Brück, Alexandra Just, Veronika Frehtman, Stephanie Löbhard, Elena Terletskaia-Ladwig, Jeremy Fry, Karin Jochims, Volker Daniel, Ottheinz Krebs, Michael Dahm, Bernard Huber, Andreas Unterberg, and Jean Rommelaere |
| Summary: | 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. |
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| Item Description: | Gesehen am 02.05.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1525-0024 |
| DOI: | 10.1016/j.ymthe.2017.08.016 |