Moleculo-biological analysis for mechanism of proliferation and differentiation in glioma cells and its clinical application

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We had already made mouse monoclonal antibodies (ONS-M21) for the antigens which were shared in both glioma and medulloblastoma (Br J Cancer 68 : 831-837,1993). Then we succeed in humanization of their antibodies (Mol Immunol, in press) and their single-chained antibodies in cooperation with Chugai Pharmaceutical Co.Ltd.Using these humanized antibodies and their single-chained antibodies, we might develop the correct diagnoses of tumor sites, and will try to apply to immunotherapy of malignant glioma patients. And now it is in the last steps to extract the malignant glioma-associated antigens which were recognized with these mouse monoclonal antibodies. After extraction of their antigens, we will identify their gene arrangement and mechanisms of their expression. On the other hand, we are researching about the gene therapy for malignant gliomas, with prof. Kazuhiro IKenaka who belong to Okazaki National Research Institutes, National Institute for Physiological Sciences. We published two papers about selective expression of foreign genes in glioma cells by glial-specific promoters (Jpn J Cancer Res 83 : 1244-1247,1992 ; J Neurosci Res 38 : 415-423,1994). At present, we repeats the in vivo gene therapy in mouse glioma models under these in vitro data with the mouse myelin basic protein (MBP) gene promoters to direct toxic gene expression (J Neurosci Res 36 : 472-479,1993). We confirmed that all mice recovered with intraperitoneal administration of GCV,if we could transduced HTK genes into approximately 25% of glioma cells implanted into the mouse brain.If we could elucidate the glioma-associated antigens according to our plans, we will analyze the promoters controlling their manifestation and will apply them in gene therapy with tissue-specificity in the future.