Transfection-induced tumor necrosis factor-alpha increases the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells: continuous expression of intercellular adhesion molecule-1 on the glioma cells.

To develop more effective adoptive immunotherapy, we transfected the human tumor necrosis factor-alpha (TNF-alpha) gene into human glioma cells (U251-SP), which were used as target cells. TNF-alpha is known to increase both the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of glioma cells and the susceptibility of glioma cells to lymphokine-activated killer (LAK) cell cytolysis. We compared the expression of ICAM-1 induced by TNF-alpha generated by the TNF-alpha gene-transfected cells with that induced by exogenously added TNF-alpha. When the TNF-alpha gene was transfected into U251-SP cells, the expression of ICAM-1 was detected on the cell surface from 3 days after the transfection and continued until at least 9 days. In contrast, it was expressed only transiently in the case of exogenously added TNF-alpha. Also, the cytolytic activity of LAK cells induced by transfection-induced TNF-alpha was significantly stronger than that induced by exogenously added TNF-alpha. The increased susceptibility was quenched by anti-ICAM-1 monoclonal antibody. These data indicated that continuous expression of ICAM-1 induced by TNF-alpha gene transfection of glioma cells resulted in higher cytolytic activity of LAK cells.