MERIT Award Recipient: Darell D. Bigner, M.D., Ph.D.
Brain Tumors - Immunological and Biological Studies
There were more than 17,000 new cases of primary malignant glioma brain tumors diagnosed in 2002, and more than 13,100 deaths. Over the last 30 years, there has been little progress in the treatment of malignant gliomas. Malignant brain tumors remain highly refractive to therapy, and current treatments produce no long-term survivors in patients with these tumors. Glioblastoma multiforme (GBM) are malignant brain tumors characterized by aggressive local infiltration and invasion of surrounding brain tissue. The limited responsiveness of these tumors to conventional modes of treatment underscores the critical need to design and test new treatments.
Dr. Bigner's goal is to continue research to further develop and evaluate antibody-based targeted therapy for brain tumors, specifically in clinical treatment for glioblastoma multiforme. Dr. Bigner will generate monoclonal antibodies (MAbs) directed against multiple cell surface molecular targets that have been shown in preliminary studies to be involved in the growth, invasive potential and/or drug resistance of malignant glioma cells. The targeting of multiple molecular defects should help address the therapeutic limitations posed by the extreme heterogeneity inherent in malignant gliomas. Dr. Bigner's hypothesis is that poor drug delivery and widespread migration of GBM cells will be overcome by using enhanced delivery of MAbs or their fragments in the form of unarmed MAbs, toxin-MAb conjugates, or radiolabeled MAb-conjugates. Elimination of tumor cells expressing the critical target molecules should result in significant survival increases in GBM patients.