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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-10-8
pubmed:abstractText
The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer gene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 x 10(8) plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 x 10(11) v.g.), and complete tumor regression was achieved in 25% of the treated animals. Importantly, the combination of rAAV-hTERTC27 and a therapeutic dose (2.5 x 10(9) PFU) of rAdv-hTERTC27 significantly augmented the therapeutic effects and led to a 38% complete tumor regression rate. In vivo optical imaging also showed that rAAV-luc/rAdv-luc cocktail vectors could synergistically enhance the early transient and latent sustained expression of luciferase, as compared to rAdv-luc and rAAV-luc alone. These findings suggest that the combination of rAAV-hTERTC27 and a therapeutic dose of rAdv-hTERTC27 is potentially a promising treatment for glioblastoma, and the rAAV/rAdv cocktail vector system warrants further development for cancer gene therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-5500
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
723-32
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Development of recombinant adeno-associated virus and adenovirus cocktail system for efficient hTERTC27 polypeptide-mediated cancer gene therapy.
pubmed:affiliation
Department of Chemistry, Institute of Molecular Biology, The University of Hong Kong, Pokfulam, Hong Kong, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't