Intratumoral expression of a fusogenic membrane glycoprotein enhances the efficacy of replicating adenovirus therapy
Ahmed, A., Jevremovic, D., Suzuki, K., Kottke, T., Thompson, J., Emery, S., Harrington, K., Bateman, A. and Vile, R. (2003) Intratumoral expression of a fusogenic membrane glycoprotein enhances the efficacy of replicating adenovirus therapy. Gene therapy, 10, (19), 1663-1671. (doi:10.1038/sj.gt.3302064).
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We describe here a novel strategy to enhance the in vivo efficacy of replicating adenovirus therapy, using coinjection of plasmid DNA encoding a fusogenic viral glycoprotein. The combination of fusogenic membrane glycoprotein (FMG)-induced tumor cell fusion and infection with replicating adenovirus effectively treats even large established tumors at doses of plasmid DNA and virus that alone are ineffective.
Adenoviral infection appears to increase the transduction of the tumor cells to a modest degree thereby boosting the FMG-mediated component of the therapy. Simultaneously, syncytial formation enhances the therapeutic effects of viral infection by increasing spread of adenoviral particles through the tumor cell population and by increasing titer of virus released from the tumor cells. This effect is due probably to release of intracellular viral particles upon tumor cell death and also to increased levels of E1A protein within syncytia, whose increased metabolic rate is associated with enhanced levels of protein expression. Cotransduction of tumor cells with replicating adenovirus and FMG-expressing vectors could either be combined within single replicating vectors or could be used in strategies using separate administration of two components, both at lower doses than required for either therapy alone.
|Digital Object Identifier (DOI):||doi:10.1038/sj.gt.3302064|
|Keywords:||syncytia, conditionally replicating adenoviruses, fusogenic membrane glycoproteins|
|Subjects:||Q Science > QR Microbiology > QR355 Virology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QH Natural history > QH426 Genetics
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||20 Apr 2006|
|Last Modified:||06 Aug 2015 02:26|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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