Yoshida J, Takaoka T, Mizuno M, Momota H, Okada H
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
J Surg Oncol. 1996 Jul;62(3):177-82. doi: 10.1002/(SICI)1096-9098(199607)62:3<177::AID-JSO6>3.0.CO;2-4.
With the aim of developing an effective immunotherapy for malignant glioma, glioma cells were incubated with tumor necrosis factor-alpha (TNF-alpha) to increase their susceptibility to lysis by lymphokine-activated killer (LAK) cells. Treatment with exogenous TNF-alpha induced the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of glioma cells. In addition, the cytolytic activity of LAK cells toward exogenous TNF-alpha treated glioma cells was significantly greater than LAK cell activity toward untreated glioma cells. This increase in cytolytic activity was blocked by anti-ICAM-1 monoclonal antibodies (MAb). Furthermore, co-treatment with a bifunctional antibody (BFA) composed of anti-CD3 (UCHT1) and antiglioma (G-22) antibodies synergistically increased the cytolytic activity of LAK cells towards TNF-alpha-treated glioma cells. These results indicate that a combination of exogenous TNF-alpha and anti-CD3/antiglioma BFA may provide an effective modified adoptive immunotherapy for patients with malignant glioma.
为了开发一种针对恶性胶质瘤的有效免疫疗法，将胶质瘤细胞与肿瘤坏死因子-α（TNF-α）一起孵育，以增加其对淋巴因子激活的杀伤细胞（LAK细胞）裂解的敏感性。用外源性TNF-α处理可诱导胶质瘤细胞表面细胞间黏附分子-1（ICAM-1）的表达。此外，LAK细胞对外源性TNF-α处理的胶质瘤细胞的细胞溶解活性明显高于其对未处理的胶质瘤细胞的活性。这种细胞溶解活性的增加被抗ICAM-1单克隆抗体（MAb）阻断。此外，由抗CD3（UCHT1）和抗胶质瘤（G-22）抗体组成的双功能抗体（BFA）联合处理可协同增加LAK细胞对TNF-α处理的胶质瘤细胞的细胞溶解活性。这些结果表明，外源性TNF-α与抗CD3/抗胶质瘤BFA联合使用可能为恶性胶质瘤患者提供一种有效的改良过继性免疫疗法。
