title: A chimeric adenovirus with an Ad 3 fiber knob modification augments glioma virotherapy.
abstract: BACKGROUND
  Malignant gliomas remain refractory to treatment despite advances in chemotherapy and surgical techniques. Viral vectors developed to treat gliomas have had low transduction capabilities, limiting their use. Gliomas over-express CD46, CD80, and CD86, all of which bind adenovirus serotype 3.
  
  
  METHODS
  To increase the infectivity and replication of oncolytic vectors in malignant brain tumors, we created a conditionally replicating adenovirus, CRAd-Survivin-5/3, which contains a survivin promoter-driving E1A and a chimeric fiber consisting of adenovirus serotype 3 knob.
  
  
  RESULTS
  In vitro, this modified CRAd showed ten- to 100-fold increased cytotoxicity against glioma cells. Ex vivo analysis of primary glioblastoma multiforme samples infected with CRAd-Survivin-5/3 showed an increase in cytotoxicity of 20-30% compared to adenovirus wild-type (AdWT). In normal human astrocytes and normal brain tissues, CRAd-Survivin-5/3 exhibited 30-40% and 10-15% lower cytotoxicity than AdWT, respectively. In an intracranial xenograft model of glioma, this oncolytic virus increased tumor-free survival and overall lifespan by 50% compared to controls (p < 0.05).
  
  
  CONCLUSIONS
  CRAd-Survivin-5/3 represents an attractive alternative to existing vectors and should be tested further in the pre-clinical setting.
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Suvobroto
authors.initials: S
authors.lastname: Nandi
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Ulasov
authors.forename: Cleo E
authors.initials: CE
authors.lastname: Rolle
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D005822:Genetic Vectors / Q000235:genetics*; D005910:Glioma / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods*
chemical_list: D008869:Microtubule-Associated Proteins
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