Gene transfer to cervical cancer with fiber-modified adenoviruses

International Journal of Cancer. Journal International Du Cancer
Daniel T ReinDavid T Curiel

Abstract

Successful adenoviral (Ad) vector-mediated strategies for cancer gene therapy mandate gene-delivery systems that are capable of achieving efficient gene delivery in vivo. In many cancer types, in vivo gene-transfer efficiency remains limited due to the low or highly variable expression of the primary Ad receptor, the coxsackie Ad receptor (CAR). In this study, we evaluated the expression of CAR on cervical cancer cells as well as CAR-independent targeting strategies to integrins (Ad5.RGD), heparan sulfate proteoglycans (Ad5.pK7) or both (Ad5.RGD.pK7). We used a panel of established cervical cancer cell lines and primary cervical cancer cells isolated from patients to quantify the expression of CAR mRNA and to evaluate the gene-transfer efficiency of fiber-modified Ads. Of the fiber-modified vectors, Ad5.pK7 and Ad5.RGD.pK7 displayed significantly enhanced gene-transfer efficiency in vitro. Gene-delivery efficiency in vivo was evaluated using an s.c. cervical cancer mouse model. Ad5.RGD.pK7 significantly improves tumor targeting in vivo, resulting in a significantly improved tumor/liver ratio in mice. Our results suggest that the double-modified Ad5.RGD.pk7 vector enhances gene transfer to clinically relevant cervical cancer sub...Continue Reading

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Citations

May 19, 2012·Cancer Gene Therapy·E N BallardR D Gerard
Jan 28, 2006·Cancer Gene Therapy·J N GlasgowD T Curiel
Feb 9, 2012·Advances in Virology·M H Verheije, P J M Rottier
Mar 25, 2006·Future Oncology·Daniel T ReinDavid T Curiel
Jul 12, 2011·Gynecologic Oncology·Daniel T ReinMartina Breidenbach
Oct 4, 2006·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Alexander StoffDavid T Curiel
Mar 14, 2007·The Journal of Gene Medicine·Sophy ZhengMaciej S Lesniak
Apr 4, 2006·Journal of Virological Methods·Chitladda MahanivongShuang Huang
Nov 29, 2005·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Kai TemmingRobbert J Kok
Jul 26, 2011·Cellular & Molecular Biology Letters·Mandy S Y LungVincent Murray
Jul 13, 2006·Expert Review of Anticancer Therapy·Rebecca A Brooks, David G Mutch
May 3, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mari RakiAkseli Hemminki
Jul 22, 2018·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Julius W KimMaciej S Lesniak
Mar 25, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Harm C A GraatTetsuo Hotta

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