Journal
JOURNAL OF VIROLOGICAL METHODS
Volume 155, Issue 1, Pages 44-54Publisher
ELSEVIER
DOI: 10.1016/j.jviromet.2008.09.020
Keywords
Cytopathogenicity; Cytotoxicity; Poliovirus; MTS-based assay; CD155; Gliomas
Funding
- National Cancer Institute, National Institutes of Health [N01-CO-12400]
- Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health
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PVS-RIPO is it recombinant oncolytic poliovirus designed for clinical application to target CD155 expressing malignant gliomas and other malignant diseases. PVS-RIPO does not replicate in healthy neurons and is therefore non-pathogenic in rodent and non-human primate models of poliomyelitis. A tetrazolium salt dye-based cellular assay was developed and qualified to define the cytotoxicity of virus preparations on susceptible cells and to explore the target cell specificity of PVS-RIPO. In this assay, PVS-RIPO inhibited proliferation of U87-MG astrocytoma cells in a dose-dependent manner. However, HEK293 cells were much less susceptible to cell killing by PVS-RIPO. In contrast, the Sabin type 1 live attenuated poliovirus vaccine strain (PV(1)S) was cytotoxic to both HEK293 and U87-MG cells. The correlation between expression of CD155 and cytotoxicity was also explored using six different cell lines. There was little or no expression of CD155 and PVS-RIPO-induced cytotoxicity in Jurkat and Daudi cells. HEK293 was the only cell line tested that showed CD155 expression and resistance to PVS-RIPO cytotoxicity. The results indicate that differential cytotoxicity measured by the colorimetric assay can be used to evaluate the cytotoxicity and cell-type specificity of recombinant strains of poliovirus and to demonstrate lot to lot consistency during the manufacture of viruses intended for clinical use. (c) 2008 Elsevier B.V. All rights reserved.
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