Analysis of aberrant EGFR in malignant gliomas, and the development of immunochemotherapy using the antibody against the receptor

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Aberrant EGFR found in malignant gliomas, have abnormalities in the extracellular domain and intracellular domain. Aberrant EGFR was found in 14 (35%)/40 glioblastomas. Eight aberrant EGFR had an abnormality in the extracellular domain, 4 had abrromality in the intracellular domain and only 2 had abnormalities in both domains. Overepression of normal EGFR eas found in 7 glioblastomas (17.5%). In 17 anaplastic gliomas, aberrant EGFR was expressed in 3 (17.6%), but aberrant EGFR was not expressed in low grade gliomas, IN the statistical analysis of the survival time, the average survival time was 440 days in 18 patients with glioblastomas showing moderate expression of normal EGFR, 354 days in 6 patients with glioblastomas showing overexpression of normal EGFR, 318 days in 11 patients with glioblastomas demonstrating aberrant EGFR.these abnormalities may have a relationship to malignancy of gliomas whth tyrosine kinase activity. We tried an antisence EGFR oligonucleotide (D-oligonucleotide) enveloped with Lipofectin^R against three malignant glioma cell lines. The antisense EGFR oligonucleotide enveloped with Lipofectin^R inhibited the proliferation in three malignant glioma cell lines from 30 to 10% after three days incubation compared as a control incubation. The DNA synthesis activity in the supressed tumor cells dropped out about 70%. This oligonucleotide also induced accumulation of tumor cells in S and G2 + M phase. An antisense EGFR oligonucleotide enveloped with Lipofectin^R was expected to become one of the best gene therapies against malignant gliomas.We are developing the monoclonal antibody to the aberrant EGFR in order to do a diagnosis of malignant gliomas and do a immunochemotheapy against malignant gliomas.