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 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.
Toda
K
K
Department of Neurosurgery, Saga Medical School, Nabeshima.
Shiraishi
T
T
Hirotsu
T
T
Fukuyama
K
K
Mineta
T
T
Kawaguchi
S
S
Tabuchi
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001932:Brain Neoplasms / Q000628:therapy*; D004249:DNA Damage; D053222:Fas Ligand Protein; D005910:Glioma / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D010844:Picibanil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D010844:Picibanil