Source:http://linkedlifedata.com/resource/pubmed/id/20410926
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2010-8-12
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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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Ganciclovir,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Urokinase Plasminogen...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/constitutive androstane receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1476-5462
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1000-10
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pubmed:dateRevised |
2011-10-11
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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
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pubmed:year |
2010
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pubmed:articleTitle |
Retargeted adenoviral cancer gene therapy for tumour cells overexpressing epidermal growth factor receptor or urokinase-type plasminogen activator receptor.
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pubmed:affiliation |
Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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