The cytocidal activity of OK-432-activated mononuclear cells against human glioma cells is partly mediated through the Fas ligand/Fas system

Abstract

We have been applying an adoptive immunotherapy protocol to patients with malignant brain tumors using OK-432-activated peripheral blood mononuclear cells (OK-MCs). In order to elucidate the mechanism of OK-MCs' cytotoxicity, we examined the expression of Fas ligand mRNA in OK-MCs and the cytocidal activity of these cells against a human glioma cell line, T98G which expresses a high level of Fas. The expression of Fas ligand mRNA was low in non treated peripheral blood mononuclear cells 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 antibody, which binds to Fas and blocks the binding of Fas ligand to Fas. These data indicate that the cytotoxic activity of OK-MCs via apoptosis seems to be at least partly mediated by the Fas ligand/Fas system. Adoptive immunotherapy using the Fas ligand/Fas system could be a new treatment modality for human malignant brain tumors.