Correlative Studies and Immune Monitoring Core

项目摘要-核心3 相关研究和免疫监测核心(核心3)将提供包括以下内容的所有三个项目 计划项目拨款建议书全面、最先进的生物信息库和免疫/分子图谱 由一组非常有成就的研究科学家提供支持，他们利用这些特定的平台 与以前和/或当前的癌症免疫治疗试验相结合。这三个项目调查了 新的免疫治疗方法治疗慢性粒细胞白血病的安全性、有效性和机制 胶质母细胞瘤(GBM)是一种预后极差的诊断。此核心的目标是确定 免疫学相关性，预测临床结果并提供机制洞察利用 全面的高度标准化和/或正式验证的分析平台。这一核心还将 提供免疫/分子图谱领导和专业知识，与生物统计和 所有项目的生物信息学核心(核心1)和临床试验和成像核心(核心2)。这是至关重要的 拟议的项目将对高级别胶质瘤进行明确、准确的诊断，这项服务将 由这个核心提供。拟议项目所需的高质量血液和组织样本将 由这个核心交付。本提案中的组织病理学服务包括肿瘤内的特征性 高分化和高级别浸润性星形细胞瘤组织谱系的异质性 根据需要对人脑胶质瘤组织进行抗原表达的诊断、分级和体外分析。这个 GBM中的CMV pp65抗原将成为靶点，我们将与CLIA认证的图像细胞术合作 实验室将开发CMV CISH检测方法，以表征CMV的存在和高级别的异质性 神经胶质瘤。此外，酷睿3将提供高度专业化和全面的分析平台，包括 免疫表型、免疫功能分析和TCR测序。我们将利用高维流动 流式细胞术在项目1及以下抗CD27治疗后是否持续Treg衰竭 在项目3中使用洛莫司汀。我们将使用多功能T细胞试验来确定抗CD27 增加疫苗诱导的CD4和CD8抗原特异性T细胞的频率和相对多功能性 细胞反应。T细胞免疫反应的评估也将使用相同的高度 在项目2和项目3中由该核心进行标准化和验证的分析。

PROJECT SUMMARY – Core 3 The Correlative Studies and Immune Monitoring Core (Core 3) will provide all three projects comprising this Program Project Grant proposal comprehensive, state-of-the-art biorepository and immune/molecular profiling support by a team of highly accomplished research scientists who have utilized these specific platforms in conjunction with previous and/or current cancer immunotherapy trials. These three projects investigate the safety, efficacy and mechanisms of novel immunotherapeutic approaches to the treatment of patients with glioblastoma (GBM), a diagnosis with extremely poor prognosis. The objectives of this Core are to identify immunologic correlatives that predict clinical outcomes and provide mechanistic insights utilizing a comprehensive repertoire of highly standardized and/or formally validated assay platforms. This Core will also provide immune/molecular profiling leadership and expertise in collaboration with the Biostatistics and Bioinformatics Core (Core 1) and the Clinical Trials and Imaging Core (Core 2) for all projects. It is critical to the proposed projects to have well defined, accurately diagnosed high grade gliomas, a service that will be provided by this core. High quality blood and tissue samples needed for the proposed projects will be delivered by this core. Histopathologic services in this proposal include characterizing intratumoral heterogeneity in a spectrum of both well-differentiated and high grade infiltrating astrocytomas via tissue diagnosis and grading and in vitro analysis of antigenic expression in human glioma tissues as needed. The CMV pp65 antigen in GBM will be targeted and we will collaborate with the CLIA-certified Image Cytometry laboratory to develop a CMV CISH assay to characterize CMV presence and heterogeneity in high grade gliomas. Additionally, Core 3 will provide highly specialized and comprehensive assay platforms that include immunophenotyping, immune function analyses, and TCR sequencing. We will utilize high dimensional flow cytometry to determine if TReg depletion is sustained after anti-CD27 treatment in Project 1 and following lomustine administration in Project 3. We will use the polyfunctional T cell assay to determine if anti-CD27 increases the frequencies and relative polyfunctionality of CD4 and CD8 antigen-specific, vaccine-induced T cell responses. Assessment of T cell immune responses will also be measured using the same highly standardized and validated assays by this core in Project 2 and Project 3.