Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-8-12
pubmed:abstractText
We have assessed the ability of bispecific fusion proteins to improve adenovirus-mediated transfer of therapeutic and marker transgenes. We constructed an expression vector that can be easily modified to synthesize a variety of fusion proteins for retargeting adenoviral gene therapy vectors to cell surface markers, which are differentially expressed between normal and cancer cells. Adenoviral transduction can be improved in a number of tumour cell lines which overexpress EGFR (epidermal growth factor receptor) or uPAR (urokinase-type plasminogen activator receptor), but which have only low levels of endogenous hCAR (human coxsackie B and adenovirus receptor) expression. Up to 40-fold improvement in beta-galactosidase transgene expression was seen using an EGFR retargeting protein, and up to 16-fold using a second fusion protein targeting uPAR. In vitro, our uPAR retargeting fusion protein improved the sensitivity to adenoviral herpes simplex virus thymidine kinase/ganciclovir by an order of magnitude, whereas in vivo, our EGFR retargeting protein is able to significantly delay tumour growth in rodent animal models in a dose-dependent manner. The 'cassette' design of our fusion protein constructs offers a flexible method for the straightforward synthesis of multiple adenoviral retargeting proteins, directed against a variety of tumour-associated antigens, for use in clinical trials.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1476-5462
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1000-10
pubmed:dateRevised
2011-10-11
pubmed:meshHeading
pubmed-meshheading:20410926-Adenoviridae, pubmed-meshheading:20410926-Antiviral Agents, pubmed-meshheading:20410926-Cell Line, Tumor, pubmed-meshheading:20410926-Drug Resistance, Neoplasm, pubmed-meshheading:20410926-Ganciclovir, pubmed-meshheading:20410926-Gene Therapy, pubmed-meshheading:20410926-Gene Transfer Techniques, pubmed-meshheading:20410926-Genetic Vectors, pubmed-meshheading:20410926-Humans, pubmed-meshheading:20410926-Membrane Proteins, pubmed-meshheading:20410926-Neoplasms, pubmed-meshheading:20410926-Protein Engineering, pubmed-meshheading:20410926-Receptor, Epidermal Growth Factor, pubmed-meshheading:20410926-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:20410926-Receptors, Urokinase Plasminogen Activator, pubmed-meshheading:20410926-Recombinant Fusion Proteins, pubmed-meshheading:20410926-Transduction, Genetic
pubmed:year
2010
pubmed:articleTitle
Retargeted adenoviral cancer gene therapy for tumour cells overexpressing epidermal growth factor receptor or urokinase-type plasminogen activator receptor.
pubmed:affiliation
Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't