TRANSFECTION-INDUCED TURNER 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 h uman tumor necrosis factor-alpha (TNF-alpha) gene into human glioma ce lls (U251-SP), which were used as target cells. TNF-alpha is known to increase both the expression of intercellular adhesion molecule-1 (ICA M-1) on the surface of glioma cells and the susceptibility of glioma c ells to lymphokine-activated killer (LAK) cell cytolysis. We compared the expression of ICAM-1 induced by TNF-alpha generated by the TNF-alp ha gene-transfected cells with that induced by exogenously added TNF-a lpha. 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 afte r the transfection and continued until at least 9 days. In contrast, i t was expressed only transiently in the case of exogenously added TNF- alpha. Also, the cytolytic activity of LAK cells induced by transfecti on-induced TNF-alpha was significantly stronger than that induced by e xogenously added TNF-alpha. The increased susceptibility was quenched by anti-ICAM-1 monoclonal antibody. These data indicated that continuo us expression of ICAM-1 induced by TNF-alpha gene transfection of glio ma cells resulted in higher cytolytic activity of LAK cells.