| Autor: |
Yang X; Bioanalytical Development Laboratory, Biopharmaceutical Development Program, SAIC-Frederick, Inc., NCI Frederick, USA., Chen E, Jiang H, Muszynski K, Harris RD, Giardina SL, Gromeier M, Mitra G, Soman G |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of virological methods [J Virol Methods] 2009 Jan; Vol. 155 (1), pp. 44-54. Date of Electronic Publication: 2008 Nov 08. |
| DOI: |
10.1016/j.jviromet.2008.09.020 |
| Abstrakt: |
PVS-RIPO is a 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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