THE CYTOCIDAL ACTIVITY OF OK-432-ACTIVATED MONONUCLEAR-CELLS AGAINST HUMAN GLIOMA-CELLS IS PARTLY MEDIATED THROUGH THE FAS LIGAND FAS SYSTEM

We have been applying an adoptive immunotherapy protocol to patients w ith malignant brain tumors using OK-432-activated peripheral blood mon onuclear cells (OK-MCs). In order to elucidate the mechanism of OK-MCs ' cytotoxicity, we examined the expression of Fas ligand mRNA in OK-MC s and the cytocidal activity of these cells against a human glioma cel l line, T98G which expresses a high level of Fas. The expression of Fa s ligand mRNA was low in non-treated peripheral blood mononuclear cell s and was elevated by treatment with OK-432, irrespective of the dose employed. Apoptosis of T98G cells induced by OK-MCs was unequivocally inhibited by the pretreatment of T98 G cells with ZB4 monoclonal antib ody, which binds to Fas and blocks the binding of Fas ligand to Fas. T hese data indicate that the cytotoxic activity of OK-MCs via apoptosis seems to be at least partly mediated by the Fas ligand/Fas system. Ad optive immunotherapy using the Fas ligand/Fas system could be a new tr eatment modality for human malignant brain tumors.