Preparing an oncolytic poliovirus recombinant for clinical application against glioblastoma multiforme

被引:40
作者
Goetz, Christian [1 ]
Gromeier, Matthias [1 ]
机构
[1] Duke Univ, Med Ctr, Div Neurosurg, Dept Surg, Durham, NC 27710 USA
关键词
PVS-RIPO; Glioblastoma multiforme; Central nervous system; RIBOSOMAL ENTRY SITE; ACTIVATED PROTEIN-KINASE; CELL-CELL ADHESION; FACTOR 4G EIF4G; TRANSLATION INITIATION; EUKARYOTIC TRANSLATION; RECEPTOR/CD155; GENE; MESSENGER-RNA; ONCOGENIC RAS; VIRUS MUTANT;
D O I
10.1016/j.cytogfr.2010.02.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PVS-RIPO is a genetically recombinant, non-pathogenic poliovirus chimera with a tumor-specific conditional replication phenotype. Consisting of the genome of the live attenuated poliovirus type 1 (Sabin) vaccine with its cognate IRES element replaced with that of human rhinovirus type 2. PVS-RIPO displays an inability to translate its genome in untransformed neuronal cells, but effectively does so in cells originating from primary tumors in the central nervous system or other cancers. Hence, PVS-RIPO unleashes potent cytotoxic effects on infected cancer cells and produces sustained anti-tumoral responses in animal tumor models. PVS-RIPO presents a novel approach to the treatment of patients with glioblastoma multiforme, based on conditions favoring an unconventional viral translation initiation mechanism in cancerous cells. In this review we summarize advances in the understanding of major molecular determinants of PVS-RIPO oncolytic efficacy and safety and discuss their implications for upcoming clinical investigations. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:197 / 203
页数:7
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