A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor

Jan E. Carette, Harm C.A. Graat, Frederik H.E. Schagen, D. C.Jeroen Mastenbroek, Marianne G. Rots, Hidde J. Haisma, Geny M.M. Groothuis, Gerard R. Schaap, Johannes Bras, Gertjan J.L. Kaspers, Paul I.J.M. Wuisman, Winald R. Gerritsen, Victor W. van Beusechem

Research output: Contribution to journalArticlepeer-review

Abstract

Virotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer.

Original languageEnglish (US)
Pages (from-to)56-67
Number of pages12
JournalVirology
Volume361
Issue number1
DOIs
StatePublished - Apr 25 2007

Keywords

  • Coxsackie and adenovirus receptor
  • Epidermal growth factor receptor
  • Gene therapy
  • Oncolytic adenovirus
  • Osteosarcoma
  • Targeting

ASJC Scopus subject areas

  • Virology

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