Regression of advanced rat and human gliomas by local or systemic treatment with oncolytic parvovirus H-1 in rat models
| Autor: | Irina Kiprianova, Jean Rommelaere, Ali Ayache, Nadja Thomas, Clemens Sommer, R. M. Koch, Marta Herrero y Calle, Karsten Geletneky, Jörg R. Schlehofer, Laurent Deleu |
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| Rok vydání: | 2010 |
| Předmět: |
H-1 parvovirus
Cancer Research Pathology medicine.medical_specialty Parvovirus H-1 Secondary infection Antibodies Viral Polymerase Chain Reaction Virus Glioma medicine Animals Humans Virotherapy Oncolytic Virotherapy biology Brain Neoplasms Parvovirus Brain medicine.disease biology.organism_classification Antibodies Neutralizing Magnetic Resonance Imaging Xenograft Model Antitumor Assays Rats Oncolytic virus Disease Models Animal Oncology Viral replication Basic and Translational Investigations DNA Viral Neurology (clinical) |
| Zdroj: | Neuro-Oncology. 12:804-814 |
| ISSN: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/noq023 |
| Popis: | Oncolytic virotherapy is a potential treatment modality under investigation for various malignancies including malignant brain tumors. Unlike some other natural or modified viruses that show oncolytic activity against cerebral neoplasms, the rodent parvovirus H-1 (H-1PV) is completely apathogenic in humans. H-1PV efficiently kills a number of tumor cells without harm to corresponding normal ones. In this study, the concept of H-1PV-based virotherapy of glioma was tested for rat (RG-2 cell-derived) and for human (U87 cell-derived) gliomas in immunocompetent and immunodeficient rat models, respectively. Large orthotopic rat and human glioma cell-derived tumors were treated with either single stereotactic intratumoral or multiple intravenous (iv) H-1PV injections. Oncolysis was monitored by magnetic resonance imaging and proven by histology. Virus distribution and replication were determined in brain and organs. In immunocompetent rats bearing RG-2-derived tumors, a single stereotactic intratumoral injection of H-1PV and multiple systemic (iv) applications of the virus were sufficient for remission of advanced and even symptomatic intracranial gliomas without damaging normal brain tissue or other organs. H-1PV therapy resulted in significantly improved survival (Kaplan-Meier analysis) in both the rat and human glioma models. Virus replication in tumors indicated a contribution of secondary infection by progeny virus to the efficiency of oncolysis. Virus replication was restricted to tumors, although H-1PV DNA could be detected transiently in adjacent or remote normal brain tissue and in noncerebral tissues. The results presented here and the innocuousness of H-1PV for humans argue for the use of H-1PV as a powerful means to perform oncolytic therapy of malignant gliomas. |
| Databáze: | OpenAIRE |
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