Antigen specific modeling of glioma immunotherapy

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): This proposal is designed to provide Dr. Andrew T. Parsa with the opportunity to develop as an academic physician and basic scientist over five years. Dr. Parsa is an Assistant Professor in the Department of Neurological Surgery at UCSF with a clinical and scientific interest in brain tumors. He is a practicing neurosurgeon who will be spending 50-60% of his academic efforts in a program of scientific training supervised by Dr. Abul Abbas, his mentor. The scientific development of Dr. Parsa will be facilitated by graduate coursework, research seminars, and a hypothesis driven research project for which Dr. Parsa will be primarily responsible as principal investigator. The project, entitled "Antigen Specific Modeling of Glioma Immunotherapy", addresses fundamental questions about immunity in the CNS. The proposed experiments are designed to test the hypothesis that local anti-tumor immunity inversely correlates with intracranial glial tumor burden. Glial cells are integrally involved in maintaining functional integrity of the nervous system. Neurological disorders can result when extra-neuronal cells such as glia transform into malignant tumors. Immunotherapy is an attractive alternative to conventional adjuvant therapy because it can specifically target malignant glial cells while preserving function of surrounding cells, including neurons. Within the context of a transgenic model of antigen specific glioma the following Specific Aims will be pursued to: 1) define the kinetics, sites and magnitude of T cell responses to intracranial glial tumor specific antigen, 2) analyze T cell accrual in the CNS after peripheral stimulation with tumor specific antigen, and 3) characterize T-cell responses against tumor specific antigen after trafficking to the CNS. Achieving these Aims will facilitate a refined understanding of antigen specific immune mediated effects against tumors of the CNS. Importantly, these Aims will allow the investigators to adapt and test a model that recapitulates the human condition of a spontaneously arising glial tumor. The focused nature of these Aims, combined with clinical and scientific environment at UCSF, will provide the PI with a valuable training experience. The long-term goal of this proposal is to facilitate the development of Dr. Parsa into an independent investigator capable of making meaningful scientific contributions.