Passive tumour targeting of polymer-coated adenovirus for cancer gene therapy

被引:49
作者
Fisher, Kerry D.
Green, Nicola K.
Hale, Ashley
Subr, Vladimir
Ulbrich, Karel
Seymour, Leonard W.
机构
[1] Univ Oxford, Dept Clin Pharmacol, Radcliffe Infirm, Oxford OX2 6HA, England
[2] Hybrid Syst Ltd, Cherwell Innovat Ctr, Upper Heyford, Oxon, England
[3] Acad Sci Czech Republic, Inst Macromol Chem, CR-16206 Prague 6, Czech Republic
基金
英国生物技术与生命科学研究理事会;
关键词
polymer-coated virus; passive targeting; cancer; virotherapy;
D O I
10.1080/10611860701501014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Adenovirus provides many opportunities as a vector for delivery of cytotoxic genes to tumours. Polymer coating of adenovirus is known to increase its plasma circulation kinetics, affording the possibility of active and passive targeting to turnouts. Here we show that polymer-coating adenovirus (pc-virus) abrogates its normal infectivity in vitro and also in liver following intravenous injection. The coated virus accumulates within solid subcutaneous AB22 mesotheliorna turnouts 40-times more than unmodified virus, and mediates higher levels of transgene expression within tumours. This is the first demonstration of passive turnour targeting of polymer-coated adenoviruses administered by intravenous injection, and also the first time pc-virus has been shown to be infectious following passive targeting to tumours in vivo. This technology provides an interesting option for delivery of therapeutic viruses to disseminated tumour masses by intravenous injection.
引用
收藏
页码:546 / 551
页数:6
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