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
Biology
Biomedical Research
Adenovirus
Fiber-chimeric
Pancreatic cancer
Serotype
adenovirus vector
bacterial enzyme
coxsackie virus and adenovirus receptor
cytosine deaminase
flucytosine
green fluorescent protein
red fluorescent protein
virus DNA
virus fiber protein
Adenovirus fiber gene
Adenovirus fiber knob 5
Adenovirus type 16
Adenovirus type 50
antineoplastic activity
article
bacterial gene
cancer cell culture
cell viability
controlled study
cytosine deaminase gene
drug cytotoxicity
drug efficacy
drug mechanism
drug specificity
fiber chimeric human adenovirus 5
gene directed enzyme prodrug therapy
gene expression
gene targeting
human
Human adenovirus
Human adenovirus 5
human cell
human tissue
liver cell culture
molecular cloning
nonhuman
pancreas adenocarcinoma
priority journal
protein domain
protein expression
suicide gene
viral gene delivery system
virus fiber
virus gene
Adenoviridae
Cell Line
Cell Line, Tumor
Flow Cytometry
Gene Therapy
Genetic Vectors
Green Fluorescent Proteins
Humans
Pancreatic Neoplasms
Polymerase Chain Reaction
Recombinant Fusion Proteins
Recombination, Genetic
Transduction, Genetic
Viral Envelope Proteins
Adenoviridae
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