Print Email Facebook Twitter Fiber-chimeric adenoviruses expressing fibers from serotype 16 and 50 improve gene transfer to human pancreatic adenocarcinoma Title Fiber-chimeric adenoviruses expressing fibers from serotype 16 and 50 improve gene transfer to human pancreatic adenocarcinoma Author Kuhlmann, K.F.D. van Geer, M.A. Bakker, C.T. Dekker, J.E.M. Havenga, M.J.E. Oude Elferink, R.P.J. Gouma, D.J. Bosma, P.J. Wesseling, J.G. TNO Kwaliteit van Leven Publication year 2009 Abstract Survival of patients with pancreatic cancer is poor. Adenoviral (Ad) gene therapy employing the commonly used serotype 5 reveals limited transduction efficiency due to the low amount of coxsackie-adenovirus receptor on pancreatic cancer cells. To identify fiber-chimeric adenoviruses with improved gene transfer, a library of Ad vectors based on Ad5 and carrying fiber molecules consisting of 16 other serotypes were transduced to human pancreatic carcinoma cell lines. Adenoviruses containing fibers from serotype 16 and 50 showed increased gene transfer and were further analyzed. In a gene-directed prodrug activation system using cytosine deaminase, these adenoviruses proved to be effective in eradicating primary pancreatic tumor cells. Fiber-chimeric Ad5 containing fiber 16 and wild-type Ad5 were also transduced ex vivo to slices of normal human pancreatic tissue and pancreatic carcinoma tissue obtained during surgery. It was shown that fiber-chimeric Ad5 with fiber 16 revealed an improved gene delivery to primary pancreatic tumor tissue compared to Ad5. In conclusion, fiber-chimeric adenoviruses carrying fiber 16 and 50 reveal a significantly enhanced gene transfer and an increased specificity to human pancreatic adenocarcinoma compared to Ad5, whereas transduction to normal pancreatic tissue was decreased. These findings expand the therapeutic window of Ad gene therapy for pancreatic cancer. © 2009 Nature Publishing Group All rights reserved. Subject BiologyBiomedical ResearchAdenovirusFiber-chimericPancreatic cancerSerotypeadenovirus vectorbacterial enzymecoxsackie virus and adenovirus receptorcytosine deaminaseflucytosinegreen fluorescent proteinred fluorescent proteinvirus DNAvirus fiber proteinAdenovirus fiber geneAdenovirus fiber knob 5Adenovirus type 16Adenovirus type 50antineoplastic activityarticlebacterial genecancer cell culturecell viabilitycontrolled studycytosine deaminase genedrug cytotoxicitydrug efficacydrug mechanismdrug specificityfiber chimeric human adenovirus 5gene directed enzyme prodrug therapygene expressiongene targetinghumanHuman adenovirusHuman adenovirus 5human cellhuman tissueliver cell culturemolecular cloningnonhumanpancreas adenocarcinomapriority journalprotein domainprotein expressionsuicide geneviral gene delivery systemvirus fibervirus geneAdenoviridaeCell LineCell Line, TumorFlow CytometryGene TherapyGenetic VectorsGreen Fluorescent ProteinsHumansPancreatic NeoplasmsPolymerase Chain ReactionRecombinant Fusion ProteinsRecombination, GeneticTransduction, GeneticViral Envelope ProteinsAdenoviridae To reference this document use: http://resolver.tudelft.nl/uuid:e4e18d30-59a0-42f8-b69b-c787b0bfb08d DOI https://doi.org/10.1038/cgt.2009.4 TNO identifier 285078 Source Cancer Gene Therapy, 16 (7), 585-597 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.