Duke SPORE in Brain Cancer

摘要--总体 建立在杜克脑瘤计划长期专注于开发、改进和测试 免疫疗法治疗低级别胶质瘤和胶质母细胞瘤(GBM)，这是Duke孢子在 脑癌继续努力开发新的或改进现有的治疗方法，以改善患有脑癌的患者的生活 原发恶性脑瘤。为了实现这一目标，该计划提供了基础设施、监督和 用于开展与这些治疗相关的创新性转化研究的资源(目标1)。创新型 建议的研究包括：1)在以下背景下研究有效的新抗原和巨细胞病毒疫苗 以CD27为靶点的调节性T细胞耗竭方法克服宿主免疫抑制 和GBM特有的抗原异质性(项目1)；2)采用新的治疗策略的研究 逆转新近发现的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的限制(项目2)； 研究一种新型细胞肿瘤疫苗策略的机制和有效性，该策略使用抗原- 负载单核细胞和内源性抗原转移途径刺激强大的抗肿瘤T细胞 答复(项目3)。为了支持这项工作，孢子通过以下三个途径确保专业知识的可用性 共享资源核心，全部来自当前奖项：生物统计学和生物信息学核心 (核心1)、临床试验运营核心(核心2)和生物信息库、病理学和免疫 监测核心(核心3)(目标2)。以孢子为主题的研究进一步得到加强 计划对发展研究的种子和实施方法的承诺 研究社区通过其发展研究和职业提升方案(目标3)。 最后，脑癌中的公爵孢子继续参与和领导孢子间活动，以 增强集体影响(目标4)。贡献包括继续领导活跃的孢子间 在免疫监测方面的合作，正在努力建立共同标准和协调分析， 并建议为NCI的新功能数据共享努力做出贡献。总而言之，公爵的大脑 孢子是解决和克服现有恶性脑瘤治疗中的局限性的理想位置 并改善集体研究环境，以推进共同的研究社区目标。

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.