Artikel
Radiation therapy enhances the oncolytic effect of Parvovirus H-1 on malignant gliomas
Gammastrahlung verstärkt den onkolytischen Effekt von Parvovirus H-1 auf maligne Gliome
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Veröffentlicht: | 11. April 2007 |
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Objective: Radiation therapy (RT) of malignant gliomas increases the survival of patients by several months but, like other standard therapies, it is unable to prevent tumor recurrence. Parvovirus H-1 (H1PV) infection leads to efficient killing of glioma cells but not of normal human astrocytes. The aim of this study was (i) to determine if previous RT could negatively affect H1PV induced oncolysis of glioma cells and (ii) to combine both treatment modalities to determine possible synergistic effects.
Methods: Primary glioblastoma cell lines NCH37, NCH 82, NCH 89 and the recurrent glioblastoma NCH 307 were exposed to RT (10Gy) and infected early (day 1) and late (day 10). These time points simulated a parallel treatment with RT and H1PV (day1) or H1PV infection after already performed RT as in recurrent GBM. Infections were performed with a multiplicity of infection (MOI) of 5 plaque forming units (pfu)/cell. Cells were counted at different days after therapy. Expression of viral non-structural protein 1 (NS1), the key mediator of cytotoxicity, was analyzed by FACS.
Results: All cell lines were susceptible to H1PV induced cell killing after previous RT. Early infection (day1) led to improved killing of relatively RT-resistant NCH37 cells (81% vs 46% without H1PV). The effect was also present but less pronounced in cells that are extremely sensitive to H1PV : NCH82 (84% cell death RT + H1PV vs. 74% H1PV) and NCH89 (89% cell death RT + H1PV vs 79% H1PV). Late infection (day 10) was less efficient than day 1, but all cells including NCH307 (recurrent GBM cell line) showed cytopathic effects (CPE) after H1PV. FACS revealed an increased number of cells positive for cytotoxis NS1 after RT and early infection.
Conclusions: H1PV has similar oncolytic effects on irradiated glioma cells as on non-irradiated counterparts The combination of RT and early H1PV infection led to increased cell killing than either therapy alone and correlated with higher NS1 expression. Thus, RT followed by early H1PV could offer a new therapeutic approach for selected patients.