Antigen specific modeling of glioma immunotherapy

神经胶质瘤免疫治疗的抗原特异性建模

• 批准号: 7276128
• 负责人: ANDREW T PARSA
• 金额: $ 16.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276128
• 关键词: Address; Adjuvant Therapy; Amino Acids; Antigens; Astrocytes; Brain Neoplasms; Cells; Central Nervous System Neoplasms; Clinical; Codon Nucleotides; Condition; Cytotoxic T-Lymphocytes; Development; Engineering; Environment; Glial Fibrillary Acidic Protein; Glioma; Glycine; Goals; Human; Immune; Immunity; Immunotherapy; Kinetics; Malignant - descriptor; Malignant Neoplasms; Mediating; Mentors; Modeling; Mutation; Nature; Nervous system structure; Neuroglia; Neurons; Neurosurgeon; Neurosurgical Procedures; Oncogenic; Peptides; Peripheral; Physicians; Principal Investigator; Research; Research Personnel; Research Project Grants; Scientist; Site; System; T-Lymphocyte; Testing; Training; Transgenic Mice; Transgenic Model; Transgenic Organisms; Tumor Antigens; Tumor Burden; Tumor Immunity; Valine; design; experience; immunogenic; interest; mouse model; nervous system disorder; professor; programs; promoter; research study; response; trafficking

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.

描述（由申请人提供）：该提案旨在为Andrew T. Parsa博士提供五年来成为学术医师和基础科学家的机会。 Parsa博士是UCSF神经外科系的助理教授，对脑肿瘤具有临床和科学兴趣。他是一名执业神经外科医生，他将在由他的导师Abul Abbas博士监督的科学培训计划中花费50-60％的学术工作。 PARSA博士的科学发展将由研究生课程，研究研讨会和假设驱动的研究项目促进，PARSA博士将主要作为首席研究员负责。该项目的标题为“神经胶质瘤免疫疗法的特定抗原建模”，涉及有关中枢神经系统免疫力的基本问题。该提出的实验旨在检验以下假设：局部抗肿瘤免疫与颅内神经胶质肿瘤负担成反比。神经胶质细胞积极参与维持神经系统的功能完整性。当神经胶质细胞（如神经胶质）转化为恶性肿瘤时，可能会导致神经系统疾病。免疫疗法是常规辅助治疗的有吸引力的替代方法，因为它可以特异性地靶向恶性神经胶质细胞，同时保留周围细胞（包括神经元）的功能。在抗原特异性神经胶质瘤的转基因模型的背景下，将采用以下特定目的：1）定义T细胞对颅内神经胶质性肿瘤特异性抗原的动力学，位点和大小的反应，2）分析T细胞在与肿瘤特异性抗体中的外围刺激后CN中的T细胞应在CNS中的T细胞应对肿瘤的特异性抗体，以及Thrim and the the the the the the the ty the the and the and them temike the the and 3）the temike the the and 3）the temike the the and 3）the temike the the the and the the和3）。实现这些目标将有助于对CNS肿瘤的抗原特异性免疫介导的作用的精致理解。重要的是，这些目标将使研究人员能够适应和测试一个模型，该模型概括了自发产生的神经胶质肿瘤的人类状况。这些目标的重点与UCSF的临床和科学环境相结合，将为PI提供宝贵的培训经验。该提案的长期目标是促进PARSA博士发展成为能够做出有意义科学贡献的独立研究人员。