Immunotherapy for glioma patients with human monoclonal antibody

Introduction: A human monoclonal antibody termed CLN-IgG, which has been secreted by a human x human hybridoma, was found to react with human glioma cells. Following the experimental studies, we applied this monoclonal antibody to patients with human gliomas. Methods: We evaluated the therapeutic effects of this monoclonal antibody and examined the chronological changes of anti-idiotypic antibody (Ab3) using ELISA method. Thirty-eight patients with malignant gliomas (Grade III and IV) and six benign glioma patients including pontine gliomas were treated with this monoclonal antibody. The age of patients varied between 8 and 79 years. CLN-igG was administered intravenously in all patients including additional intratumoral injection through an Ommayaʹs reservoir in 6 patients. Results: Of 16 patients who had been given CLN-IgG over one year, 10 patients showed good response as well as the inhibitory effects of tumor growth by CT or MRI over 12 months without any complications or clinical side effects. No complete response was noticed, but 3 patients showed partial response, 1 patient showed minor response, 32 patients were not changed for several months, 8 patients had progressive diseases by CT or MRI. Analysis of lymphocyte subsets revealed increasing tendency of T/B ratio and NK cell ratio during treatment. Anti-anti-idiotypic CLN-IgG was identified in the patientsʹ serum in 18 out of 36 patients. In 16 patients who had been given CLN-IgG over one year, mean survival time of 11 patients who had recognized Ab3 was 902 days, while that of 5 patients who had not detected Ab3 was 572 days. Conclusions: The results of our clinical study suggest an effectiveness of selective immuno-therapy for human gliomas with possible idiotypic network and this monoclonal antibody is quite useful as a maintenance therapy for glioma patients without any side effects.