Regression of advanced rat and human gliomas by local or systemic treatment with oncolytic parvovirus H-1 in rat models

• Verfasst von: Geletneky, Karsten [VerfasserIn]
• Verfasst von: Kiprianova, Irina [VerfasserIn]
• Verfasst von: Ayache, Ali [VerfasserIn]
• Verfasst von: Koch, Regina [VerfasserIn]
• Verfasst von: Herrero y Calle, Marta [VerfasserIn]
• Verfasst von: Deleu, Laurent [VerfasserIn]
• Verfasst von: Sommer, Clemens [VerfasserIn]
• Verfasst von: Thomas, Nadja [VerfasserIn]
• Verfasst von: Rommelaere, Jean [VerfasserIn]
• Verfasst von: Schlehofer, Jörg R. [VerfasserIn]
• Titel: Regression of advanced rat and human gliomas by local or systemic treatment with oncolytic parvovirus H-1 in rat models
• Verf.angabe: Karsten Geletneky, Irina Kiprianova, Ali Ayache, Regina Koch, Marta Herrero y Calle, Laurent Deleu, Clemens Sommer, Nadja Thomas, Jean Rommelaere, and Jörg R. Schlehofer
• E-Jahr: 2010
• Jahr: March 18, 2010
• Umfang: 11 S.
• Fussnoten: Gesehen am 24.02.2024
• Titel Quelle: Enthalten in: Neuro-Oncology
• Ort Quelle: Oxford : Oxford Univ. Press, 1999
• Jahr Quelle: 2010
• Band/Heft Quelle: 12(2010), 8, Seite 804-814
• ISSN Quelle: 1523-5866
• DOI: doi:10.1093/neuonc/noq023
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1837426082

Abstract

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.