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Targeting head and neck cancer by GM-CSF-mediated gene therapy in vitro.
Anticancer Research 1999 November
BACKGROUND: The prognosis for patients with squamous cell carcinoma of the head and neck (SCCHN) has remained poor during the last decades, emphasizing the need for new treatment modalities. Consequently, the objective of our study was to evaluate the feasibility and efficacy of cytokine-mediated gene therapy in SCCHN in vitro.
MATERIALS AND METHODS/RESULTS: The SCCHN cell line PCI-1 was transduced by lipofection with a plasmid encoding the human granulocytemacrophage colony-stimulating factor (GM-CSF). Transfection of PCI-1 resulted in the production of significant amounts of GM-CSF as tested by ELISA. Enhanced proliferation of a GM-CSF sensitive cell line, TF-1, after incubation with supernatants of GM-CSF-transduced tumor cells demonstrated the release of biological active GM-CSF from these PCI-1 cells. In addition, GM-CSF-secreting PCI-1 cells enhanced antitumor cytotoxicity of allogeneic peripheral blood mononuclear cells, as tested in 24h-MTT-cytotoxicity assays.
CONCLUSIONS: Our data demonstrate the feasibility and efficacy of GM-CSF-mediated stimulation of the antitumor immune response against SCCHN in vitro and may help to define new strategies in the treatment of this malignancy.
MATERIALS AND METHODS/RESULTS: The SCCHN cell line PCI-1 was transduced by lipofection with a plasmid encoding the human granulocytemacrophage colony-stimulating factor (GM-CSF). Transfection of PCI-1 resulted in the production of significant amounts of GM-CSF as tested by ELISA. Enhanced proliferation of a GM-CSF sensitive cell line, TF-1, after incubation with supernatants of GM-CSF-transduced tumor cells demonstrated the release of biological active GM-CSF from these PCI-1 cells. In addition, GM-CSF-secreting PCI-1 cells enhanced antitumor cytotoxicity of allogeneic peripheral blood mononuclear cells, as tested in 24h-MTT-cytotoxicity assays.
CONCLUSIONS: Our data demonstrate the feasibility and efficacy of GM-CSF-mediated stimulation of the antitumor immune response against SCCHN in vitro and may help to define new strategies in the treatment of this malignancy.
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