Transfection‐induced Tumor Necrosis Factor‐α 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

Abstract

To develop more effective adoptive immunotherapy, we transfected the human tumor necrosis factor‐α (TNF‐α) gene into human glioma cells (U251‐SP), which were used as target cells. TNF‐α 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‐α generated by the TNF‐α gene‐transfected cells with that induced by exogenously added TNF‐α. When the TNF‐α 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‐α. Also, the cytolytic activity of LAK cells induced by transfection‐induced TNF‐α was significantly stronger than that induced by exogenously added TNF‐α. The increased susceptibility was quenched by anti‐ICAM‐1 monoclonal antibody. These data indicated that continuous expression of ICAM‐1 induced by TNF‐α gene transfection of glioma cells resulted in higher cytolytic activity of LAK cells.