Duke SPORE in Brain Cancer

杜克孢子在脑癌中的应用

基本信息

批准号：
10248310
负责人：
FRANCIS ALI-OSMAN
金额：
$ 143.23万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-24 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10248310
关键词：
Address Agonist Antibodies Antigens Award Basic Science Bioinformatics Biological Assay Biometry Bone Marrow Brain Brain Neoplasms Cancer Etiology Cancer Vaccines Cessation of life Clinical Clinical Trials Collaborations Communication Communities Complementary therapies Cytomegalovirus Vaccines Data Commons Development Ensure Environment Epitopes Evaluation Excision FLT3 ligand Faculty Feeds Fostering Future Glioblastoma Glioma Goals Heterogeneity Human Immune Immune response Immunobiology Immunologic Monitoring Immunosuppression Immunotherapeutic agent Immunotherapy Infrastructure Lead Leadership Licensing Life Link Lymphopenia Malignant - descriptor Malignant neoplasm of brain Mus Outcome Pathology Pathway interactions Patients Pilot Projects Population Positioning Attribute Primary Brain Neoplasms Qi Recording of previous events Regulatory T-Lymphocyte Renal carcinoma Reporting Research Research Project Grants Resource Sharing Resources Sampling Scientist Seeds Surface T cell response T-Cell Depletion T-Lymphocyte Testing Therapeutic Trials Tissues Toxic effect Translational Research Universities Vaccination Vaccines Variant Work biobank career childhood cancer mortality clinical translation design immunogenic improved innovation melanoma monocyte mutant neoantigen vaccine neoantigens neuro-oncology novel novel strategies novel therapeutic intervention oncology program operation patient population predictive marker programs recruit response small molecule inhibitor therapy development translational impact translational physician tumor young adult

项目摘要

ABSTRACT – Overall Building on the Duke Brain Tumor Program's longstanding focus on development, refinement, and testing of immunotherapies to treat low-grade gliomas and glioblastoma (GBM), this renewal of the Duke SPORE in Brain Cancer continues work to develop new or improve existing therapies to improve the life of patients with primary malignant brain tumors. To achieve this goal, the Program provides the infrastructure, oversight, and resources to conduct innovative translational research relevant to these treatments (Aim 1). Innovative research proposed includes: 1) studies of potent neoantigen and Cytomegalovirus vaccines in the context of regulatory T cell depletion using a novel approach targeting CD27 to overcome both host immunosuppression and antigenic heterogeneity endemic to GBM (Project 1); 2) studies employing a novel therapeutic strategy to reverse the recently discovered phenomenon of T cell sequestration in patients with GBM and overcome the limitations imposed on immunotherapy by longstanding lymphopenia in this population (Project 2); and 3) studies examining the mechanisms and efficacy of a novel cellular tumor vaccine strategy that uses antigen- loaded monocytes and an endogenous antigen transfer pathway to stimulate potent anti-tumor T cell responses (Project 3). To support this work, the SPORE ensures the availability of expertise through three Shared Resource Cores, all continued from the current award: a Biostatistics and Bioinformatics Core (Core 1), Clinical Trial Operations Core (Core 2), and a Biorepository, Pathology, and Immune Monitoring Core (Core 3) (Aim 2). Research central to the theme of the SPORE is further enhanced by the Program's commitment to seeding developmental research and implementing approaches to grow the research community through its Developmental Research and Career Enhancement Programs (Aim 3). Finally, the Duke SPORE in Brain Cancer continues to participate in and lead inter-SPORE activities to enhance collective impact (Aim 4). Contributions include continuing leadership of an active inter-SPORE collaboration in Immune Monitoring that is working to establish common standards and to harmonize assays, and proposed contributions to the NCI's new Functional Data Commons effort. Taken together, the Duke Brain SPORE is ideally positioned to address and overcome limitations in existing malignant brain tumor therapies and enhance collective research environment to advance shared research community goals.

摘要 – 总体建立在杜克脑肿瘤项目长期致力于开发、完善和测试的基础上治疗低级别胶质瘤和胶质母细胞瘤 (GBM) 的免疫疗法，Duke SPORE 的更新脑癌继续致力于开发新的或改进现有的疗法，以改善脑癌患者的生活为了实现这一目标，该计划提供了基础设施、监督和支持。创新开展与这些治疗相关的转化研究的资源（目标 1）。拟议的研究包括：1）在以下背景下对有效的新抗原和巨细胞病毒疫苗进行研究使用靶向 CD27 的新方法消除调节性 T 细胞以克服宿主免疫抑制 GBM 特有的抗原异质性（项目 1）研究采用了一种新的治疗策略逆转最近发现的 GBM 患者 T 细胞隔离现象并克服该人群中长期存在的淋巴细胞减少症对免疫治疗造成的限制（项目 2）和 3）；研究检查了一种新型细胞肿瘤疫苗策略的机制和功效，该策略使用抗原负载的单核细胞和内源性抗原转移途径可刺激有效的抗肿瘤 T 细胞为了支持这项工作，SPORE 通过三个方面确保提供专业知识。共享资源核心，全部延续当前奖项：生物统计学和生物信息学核心（核心 1）、临床试验操作核心（核心 2）以及生物样本库、病理学和免疫监测核心（核心 3）（目标 2）进一步加强了 SPORE 主题的研究。该计划致力于开展发展研究并实施方法来培育研究界通过其发展研究和职业提升计划（目标 3）。最后，脑癌杜克 SPORE 继续参与并领导 SPORE 间活动增强集体影响力（目标 4）。贡献包括继续领导 SPORE 之间的积极活动。免疫监测方面的合作正在努力建立共同标准并协调化验，并提议为 NCI 的新功能数据共享工作做出贡献，即杜克大学大脑。 SPORE 非常适合解决和克服现有恶性脑肿瘤疗法的局限性改善集体研究环境，以推进共同的研究社区目标。