Linked Life Data

17178881

Source:http://linkedlifedata.com/resource/pubmed/id/17178881

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pubmed-article:17178881pubmed:abstractTextAmong the best-characterized genetic alterations in gliomas is the amplification of the epidermal growth factor receptor (EGFR) gene, present in approximately 40% of glioblastoma multiforme, and frequently associated with the EGFRvIII gene rearrangement. We have previously shown that attenuated vaccine strains of measles virus have potent antitumor activity against gliomas, and identified H protein mutations, which ablate recognition of the natural measles virus receptors CD46 and SLAM. Retargeted recombinant viruses were generated from the measles Edmonston-NSe vaccine strain displaying a single-chain antibody against EGFRvIII at the COOH terminus of H and containing the marker green fluorescent protein (GFP) gene in position 1. Two different H mutants were employed: H(SNS) (V451S, Y481N, and A527S)-CD46 blind, and H(AA) (Y481A and R533A)-CD46 and SLAM blind. MV-GFP virus was used as a positive control. Both EGFRvIII-retargeted viruses had significant antitumor activity against EGFRvIII-expressing glioblastoma multiforme but no cytopathic effect against normal cells. In an orthotopic model of EGFRvIII-expressing GBM39 xenografts, there was comparable therapeutic efficacy between retargeted strains and unmodified MV-GFP and statistically significant prolongation of survival in treated animals compared with the control group (P = 0.001). Formation of syncytia was observed in tumors treated with retargeted viruses, with a surrounding infiltrate consisting of macrophages and natural killer cells. In summary, EGFRvIII-retargeted oncolytic measles virus strains have comparable therapeutic efficacy with the unmodified MV-GFP strain against EGFRvIII-expressing glioma lines and xenografts with improved therapeutic index, a finding with potential translational implications in glioma virotherapy.lld:pubmed
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pubmed-article:17178881pubmed:articleTitleRetargeted oncolytic measles strains entering via the EGFRvIII receptor maintain significant antitumor activity against gliomas with increased tumor specificity.lld:pubmed
pubmed-article:17178881pubmed:affiliationMolecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.lld:pubmed
pubmed-article:17178881pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:17178881pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:17178881pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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