[en] We investigated the variability in infectivity of cells in primary brain tumor samples from different patients using an HSV-1 amplicon vector. We studied the infectivity of HSV-1 amplicon vectors in tumor samples derived from neurosurgical resections of 20 patients. Cells were infected with a definite amount of HSV-1 amplicon vector HSV-GFP. Transduction efficiency in primary tumor cell cultures was compared to an established human glioma line. Moreover, duration of transgene expression was monitored in different tumor cell types. All primary cell cultures were infectable with HSV-GFP with variable transduction efficiencies ranging between 3.0 and 42.4% from reference human Gli36 Delta EGFR glioma cells. Transduction efficiency was significantly greater in anaplastic gliomas and meningiomas (26.7+/-17.4%) compared to more malignant tumor types (glioblastomas, metastases; 11.2+/-8.5%; P=0.05). To further investigate the possible underlying mechanism of this variability, nectin-1/HevC expression was analyzed and was found to contribute, at least in part, to this variability in infectability. The tumor cells expressed the exogenous gene for 7 to 61 days with significant shorter expression in glioblastomas (18+/-13 d) compared to anaplastic gliomas (42+/-24 d; P<0.05). Interindividual variability of infectivity by HSV-1 virions might explain, at least in part, why some patients enrolled in gene therapy for glioblastoma in the past exhibited a sustained response to HSV-1-based gene- and virus therapy. Infectivity of primary tumor samples from respective patients should be tested to enable the development of efficient and safe herpes vector-based gene and virus therapy for clinical application.
Disciplines :
Neurology
Author, co-author :
Rueger, M A; Department of Neurology, University of Cologne, Max-Planck Institute for Neurological Research, Center for Molecular Medicine, European Molecular Imaging Laboratory, Cologne 50931, Germany
Winkeler, A; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Miletic, H; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Kaestle, C; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Richter, R; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Schneider, G; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Hilker, R; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
HENEKA, Michael ; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Ernestus, R I; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Hampl, J A; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Fraefel, C; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
Jacobs, A H; Department of Neurology, University of Cologne, Max-Planck Inst. for Neurol. Res., Cologne 50931, Germany
External co-authors :
yes
Language :
English
Title :
Variability in infectivity of primary cell cultures of human brain tumors with HSV-1 amplicon vectors.
This work was supported in part by the Ministerium für Schule, Wissenschaft und Forschung NRW (MSWF 516-40000299), the Center for Molecular Medicine Cologne (CMMC-TV46), the Max-Planck Society, Germany and Sixth FW EU Grant EMIL (LSHC-CT-2004-503569).
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