During the 5 year period in this proposal, the author outlines a plan to develop the skills and knowledge required to function as a competent neurosurgical clinician, investigator and teacher with a special expertise in the area of neuroonocology.
Three specific aims are described; to gain experience in the surgical and non-surgical management of patients with primary brain tumors, to develop a multidisciplinary teaching program in neurooncology and to establish a basic neurooncology laboratory. To achieve the last of these goals, a detailed 5 year research plan is submitted. During the first 2 years, 8 murine monoclonal antibodies reacting with distinctive glioma-associated antigens will be tested for localization properties in vivo against human gliomas growing subcutaneously in athymic mice and intracranially in immune-suppressed rats. Fab fragments will be compared to whole immunoglobulin and the optimal route of administration, intravenous, intracarotid, intacarotid with hyperosmotic blood-brain-barrier disruption, or direct intracranial injection will be evaluated. Using the optimal route of administration for the antibodies or the Fab fragments with the maximal localizing properties, toxicity studies will then be performed in nonhuman primates. Following extensive animal studies, a Phase I human trial to evaluate the efficacy and safety of administering internal radiation therapy to gliomas with radiolabeled monoclonal antibodies is tentatively planned.
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