In vitro and in vivo activities of an oncolytic adenoviral vector designed to express GM-CSF

Mol Ther. 2003 Jun;7(6):755-64. doi: 10.1016/s1525-0016(03)00103-5.


Oncolytic adenoviruses are being tested as biological cancer therapeutics. Ar6pAE2fF (E2F vector) contains the E2F-1 promoter to regulate the expression of the E1a gene in cells with a disregulated retinoblastoma pathway. Ar6pAE2fmGmF (E2F-GM vector) includes the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene to enhance anti-tumor activity. Both vectors selectively killed human tumor cells in vitro. The E2F-GM vector expressed biologically active murine GM-CSF in vitro and GM-CSF was detected for several days in serum and tumor extracts following injections of established human xenograft tumors. In vivo, both vectors showed significant dose-dependent anti-tumor responses. The E2F-GM vector elicited greater efficacy compared to the E2F vector, demonstrating that GM-CSF enhanced the anti-tumor activity, even in immunodeficient nude mice. Histological analysis showed that both vectors induced necrosis and mononuclear cell infiltration, but only the E2F-GM vector resulted in eosinophil infiltration. Vector replication in vivo was demonstrated. The data showed that intratumoral injection of a GM-CSF-armed oncolytic vector induced potent anti-tumor responses in xenograft tumor models, likely as the result of both oncolytic vector activity and the induction of GM-CSF-mediated inflammation and innate immunity.

MeSH terms

  • Adenoviridae / physiology*
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / therapy
  • Carcinoma, Hepatocellular / virology*
  • Cell Cycle Proteins*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / genetics
  • Liver Neoplasms / therapy
  • Liver Neoplasms / virology*
  • Mice
  • Mice, Nude
  • Promoter Regions, Genetic
  • Transcription Factors / genetics*
  • Tumor Cells, Cultured
  • Virus Replication
  • Xenograft Model Antitumor Assays


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • Transcription Factors
  • Granulocyte-Macrophage Colony-Stimulating Factor