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


METHODS
Experimental animal research.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Day
K V
KV
Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, 16 South Eutaw Street, Baltimore, MD 21201, USA.
Li
D
D
Liu
S
S
Guo
M
M
O'Malley
B W
BW
D000256:Adenoviridae; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000628:therapy*; D007376:Interleukin-2 / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D018139:Simplexvirus / Q000201:enzymology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013937:Thymidine Kinase / Q000008:administration & dosage
D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013937:Thymidine Kinase