Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models

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Show simple item record Voeks, D Martiniello-Wilks, R Madden, V Smith, K Bennetts, E Both, GW Russell, PJ 2012-02-02T07:57:25Z 2002
dc.identifier.citation Gene Therapy, 2002, 9 (12), pp. 759 - 768
dc.identifier.issn 0969-7128
dc.identifier.other C1UNSUBMIT en_US
dc.description.abstract A gene-directed enzyme pro-drug therapy (GDEPT) based on purine nucleoside phosphorylase (PNP), that converts the prodrug, fludarabine to 2-fluoroadenine, has been described, but studies are limited compared with other GDEPTs. We investigated the in vitro and in vivo efficacies of PNP-GDEPT for treating androgen-independent (AI) prostate cancer. The PNP gene controlled by Rous sarcoma virus (RSV) constitutive promoter was delivered using a recombinant ovine adenovirus vector (OAdV220) that uses a different receptor from human adenovirus type 5. In vitro, OAdV220 provided increased transgene expression over a comparable human Ad5 vector in infected AI, murine RM1 prostate cancer cells. Subsequent in vivo testing was therefore confined to OAdV220. Transduction of RM1 cells with OAdV220 before implantation in immunocompetent mice dramatically inhibited subcutaneous (s.c.) tumor growth when fludarabine phosphate was administered systemically and increased mouse survival in a dose-dependent manner. In tumor-bearing C57BL/6 mice, a single intratumoral injection of OAdV220 produced detectable PNP activity for at least 6 days and with prodrug, retarded the growth of aggressive RM1 s.c. tumors by 35% at day 14. There was a consistent trend to reduction of pre-established intraprostatic RM1 tumors. A similar regimen induced significant therapeutic efficacy in human PC3 xenografts. Thus, ovine adenovirus-mediated GDEPT using the PNP system was effective in vivo against AI prostate cancers, the aggressive murine RM1, and the human PC3 lines. Methods that improve viral dissemination and stimulate the immune system in vivo may further improve efficacy.
dc.language eng
dc.relation.isbasedon 10.1038/
dc.title Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models
dc.type Journal Article
dc.description.version Published
dc.parent Gene Therapy
dc.journal.volume 12
dc.journal.volume 9
dc.journal.number 12 en_US
dc.publocation London, UK en_US
dc.identifier.startpage 759 en_US
dc.identifier.endpage 768 en_US SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 0604 Genetics
dc.personcode 100485
dc.personcode 106503
dc.percentage 100 en_US Genetics en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US en_US
dc.location.activity ISI:000175961700001 en_US
dc.description.keywords Gene-directed enzyme prodrug therapy
dc.description.keywords Ovine adenovirus
dc.description.keywords PC3 cells
dc.description.keywords RM1 cell line
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Arts and Social Sciences
pubs.organisational-group /University of Technology Sydney/Faculty of Arts and Social Sciences/Education Group
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Strength - Health Technologies
utslib.copyright.status Closed Access 2015-04-15 12:17:09.805752+10
pubs.consider-herdc false
utslib.collection.history Closed (ID: 3)
utslib.collection.history School of Medical and Molecular Sciences (ID: 341)

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