Granulocyte-macrophage colony-stimulating factor in a combination gene therapy strategy for head and neck cancer.

Abstract

Gene therapy offers a new approach for treatment of head and neck squamous cell carcinoma (HNSCC). This study examined the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination gene therapy strategy against HNSCC in an orthotopic mouse model. Experimental animal research. Established tumors were treated with recombinant adenovirus constructs containing the genes for murine granulocyte-macrophage colony-stimulating factor (Ad-mGM-CSF), murine interleukin 2(Ad-mIL-2), or herpes simplex virus thymidine kinase (Ad-tk). The combination of Ad-mGM-CSF or Ad-mIL-2 and Ad-tk resulted in significantly greater reduction in tumor size versus other treatment groups or control subjects. There was no statistical significance between the triple combination of Ad-mGM-CSF, Ad-mIL-2, and Ad-tk versus Ad-mIL-2 and Ad-tk at 1 to 2 weeks after treatment. There was no tumor reduction seen from Ad-mGM-CSF alone and no additional benefit seen from Ad-mGM-CSF combinations in long-term follow-up studies. The greatest cytotoxic T-lymphocyte and natural killer cell activity occurred in the combination Ad-mIL-2 and Ad-tk groups with and without Ad-mGM-CSF. Results suggest that the additional mGM-CSF did not enhance the immunogenicity of the HNSCC. Optimal activation of T lymphocytes may require additional co-stimulatory molecules to stabilize the interaction of the T lymphocyte and antigen presenting cell. The presence of major histocompatibility complex Class II may increase CD4+ T-cell mediated immunogenicity and augment therapeutic antitumor immune responses in combination with tk, mIL-2, and mGM-CSF.