IMMU-09. IDENTIFICATION OF A NEW THERAPEUTIC ANTIGEN FOR GLIOBLASTOMA USING A MONOCLONAL ANTIBODY LIBRARY FROM PATIENT-DERIVED TUMOR SPHERES

Abstract

Abstract Glioblastoma (GBM) has a poor prognosis despite intensive treatment by surgery, radiation, and chemotherapy, thus new treatment strategies are urgently needed. Various innovative cancer therapies targeting cancer-specific cell surface antigens, such as chimeric antigen receptor T cell therapy, are developed and more cell surface antigens that is highly specific for GBM cells are needed. Although extensive transcriptome analyses or proteomic analysis of GBM cells were performed, few transcripts specific for GBM cells have been identified. However, GBM cell-specific antigen epitopes formed by post-translational modifications of proteins may have been missed by transcriptome or proteomic analysis, and could still be discovered by thoroughly searching for cancer-specific monoclonal antibodies. In this study, we aim to identify GBM-specific antigens using a monoclonal antibody library from patient-derived tumor spheres. Approximately 25,000 monoclonal antibody-producing hybridomas were establishment using Balb/c mice and patient derived tumor spheres. Among them, two antibodies that bind to glioblastomas and not to normal brain cells were selected and we identified the antigen by the expression cloning method. The antigen is a cell adhesion molecule and has been reported to be involved in the progression of solid tumors and is expected to be a tumor-specific antigen. These results indicate that the strategy shown in this study is useful for identifying antigens that are potentially useful as targets for GBM therapy.