CYTOLYSIS OF MALIGNANT GLIOMA-CELLS BY LYMPHOKINE-ACTIVATED KILLER-CELLS COMBINED WITH ANTI-CD3 ANTIGLIOMA BIFUNCTIONAL ANTIBODY AND TUMOR-NECROSIS-FACTOR-ALPHA/

With the aim of developing an effective immunotherapy for malignant gl ioma, glioma cells were incubated with tumor necrosis factor-alpha (TN F-alpha) to increase their susceptibility to lysis by lymphokine-activ ated killer (LAK) cells. Treatment with exogenous TNF-alpha induced th e expression of intercellular adhesion molecule-1 (ICAM-1) on the surf ace of glioma cells. In addition, the cytolytic activity of LAK cells toward exogenous TNF-ol-treated glioma cells was significantly greater than LAK cell activity toward untreated glioma cells. This increase i n cytolytic activity was blocked by anti-ICAM-1 monoclonal antibodies (MAb). Furthermore, co-treatment with a bifunctional antibody (BFA) co mposed of anti-CD3 (UCHT1) and antiglioma (G-22) antibodies synergisti cally increased the cytolytic activity of LAK cells towards TNF-alpha- treated glioma cells. These results indicate that a combination of exo genous TNF-alpha and anti-CD3/antiglioma BFA may provide an effective modified adoptive immunotherapy for patients with malignant glioma. (C ) 1996 Wiley-Liss, Inc.