The administration of IL-12/GM-CSF and Ig-4-1BB ligand markedly decreases murine floor of mouth squamous cell cancer

Otolaryngol Head Neck Surg. 2008 Sep;139(3):442-8. doi: 10.1016/j.otohns.2008.05.001.


Objective: To assess immune-based gene therapy in a murine floor of mouth (FOM) squamous cell carcinoma (SCC) model.

Study design: In vitro and in vivo testing of immune therapy for SCC.

Methods: Multiple SCC lines were infected by using advRSV-interleukin-12 (IL-12) and advCMV-interleukin-12/granulocyte macrophage colony-stimulating factor (IL-12/GM-CSF) and monitored for production of IL-12 and GM-CSF. Intratumoral injections of viral vectors were administered with systemic Ig-4-1BB ligand in an orthotopic murine FOM SCC model and followed for tumor size and survival.

Results: In vitro, all cell lines produced substantial levels of IL-12 and GM-CSF. In vivo, tumors treated with advCMV-IL-12/GM-CSF and Ig-4-1BBL showed a striking reduction in tumor volume (vs control P<0.0001) and improved median survival (38 days vs 19 days for control, P<0.0001).

Conclusion: Combination immune-based therapies effectively improve survival in mice bearing FOM SCC over single-modality therapy.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / therapy*
  • Drug Synergism
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Therapy / methods*
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Immunotherapy / methods
  • Interleukin-12 / administration & dosage*
  • Mice
  • Mouth Floor
  • Mouth Neoplasms / therapy*
  • Time Factors
  • Tumor Cells, Cultured


  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor