Tumor Necrosis Factor‐α Gene Transfer Augments Anti‐Fas Antibody‐mediated Apoptosis in Human Glioma Cells

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Abstract
To effectively induce apoptosis in human glioma cells, we tried to transfer the tumor necrosis factor (TNF)‐α gene into glioma cells to produce TNF‐α locally in these cells. The stable transfectants of three gliorna cells (U251‐SP, U251‐MG, and T98G) were resistant to exogenous TNF‐α, but their cell surface expression of the Fas antigen was dramatically enhanced by about 10 to 100‐fold as compared with untransfected glioma cells exposed to exogenous TNF‐α. The Fas antigen is a transmemhrane cytokine receptor protein of the nerve growth factor/TNF receptor superfamily. Although the untransfected glioma cells tested were resistant to anti‐Fas antibody‐mediated apoptosis, the TNF‐α gene‐transfected glioma cells exhibited high susceptibility to anti‐Fas antibody‐mediated apoptosis. Thus, TNF‐α gene transfer combined with anti‐Fas antibodies may be useful for the treatment of malignant glioma.