A chimeric adenovirus with an Ad 3 fiber knob modification augments glioma virotherapy

Suvobroto Nandi, Ilya V. Ulasov, Cleo E. Rolle, Yu Han, Maciej S. Lesniak

Research output: Contribution to journalArticle

17 Scopus citations

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 tumorfree 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.

Original languageEnglish (US)
Pages (from-to)1005-1011
Number of pages7
JournalJournal of Gene Medicine
Volume11
Issue number11
DOIs
StatePublished - 2009

Keywords

  • Adenovirus
  • Brain tumor
  • Glioma
  • Survivin
  • Virotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'A chimeric adenovirus with an Ad 3 fiber knob modification augments glioma virotherapy'. Together they form a unique fingerprint.

Cite this