Takaoka T, Yoshida J, Mizuno M, Sugita K
Department of Neurosurgery, Nagoya University School of Medicine.
Jpn J Cancer Res. 1994 Jul;85(7):750-5. doi: 10.1111/j.1349-7006.1994.tb02424.x.
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.
为了开发更有效的过继性免疫疗法，我们将人肿瘤坏死因子-α（TNF-α）基因转染到人胶质瘤细胞（U251-SP）中，这些细胞用作靶细胞。已知TNF-α可增加胶质瘤细胞表面细胞间黏附分子-1（ICAM-1）的表达以及胶质瘤细胞对淋巴因子激活的杀伤（LAK）细胞溶解的敏感性。我们比较了由TNF-α基因转染细胞产生的TNF-α诱导的ICAM-1表达与外源性添加TNF-α诱导的ICAM-1表达。当TNF-α基因转染到U251-SP细胞中时，转染后3天在细胞表面检测到ICAM-1的表达，并持续至少9天。相比之下，在外源性添加TNF-α的情况下，ICAM-1仅短暂表达。此外，转染诱导的TNF-α诱导的LAK细胞的细胞溶解活性明显强于外源性添加的TNF-α诱导的细胞溶解活性。抗ICAM-1单克隆抗体消除了增加的敏感性。这些数据表明，胶质瘤细胞TNF-α基因转染诱导的ICAM-1持续表达导致LAK细胞具有更高的细胞溶解活性。
