Tumor necrosis factor-alpha gene transfer augments anti-Fas antibody-mediated apoptosis in human glioma cells.

To effectively induce apoptosis in human glioma cells, we tried to transfer the tumor necrosis factor (TNF)-alpha gene into glioma cells to produce TNF-alpha locally in these cells. The stable transfectants of three glioma cells (U251-SP, U251-MG, and T98G) were resistant to exogenous TNF-alpha, 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-alpha. The Fas antigen is a transmembrane 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-alpha gene-transfected glioma cells exhibited high susceptibility to anti-Fas antibody-mediated apoptosis. Thus, TNF-alpha gene transfer combined with anti-Fas antibodies may be useful for the treatment of malignant glioma.