Correlative Studies and Immune Monitoring Core

项目概要-核心3 相关研究和免疫监测核心（核心3）将提供所有三个项目，包括 计划项目资助提案全面、最先进的生物储存库和免疫/分子分析 由一个高度成就的研究科学家团队支持，他们利用这些特定的平台， 与先前和/或当前的癌症免疫治疗试验相结合。这三个项目调查了 新的免疫治疗方法的安全性、有效性和机制 胶质母细胞瘤（GBM），一种预后极差的诊断。本核心的目标是确定 免疫相关物，其预测临床结果并利用免疫相关物提供机制见解， 高度标准化和/或正式验证的分析平台的全面库。该核心还将 与生物统计学合作，提供免疫/分子分析领导力和专业知识， 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）。至关重要 拟议的项目有明确的，准确诊断的高级别胶质瘤，一项服务， 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 由这个核心传递。该提案中的组织学服务包括表征肿瘤内 高分化和高级别浸润性星形细胞瘤组织异质性 诊断和分级以及根据需要在人胶质瘤组织中进行抗原表达的体外分析。的 GBM中的CMV pp 65抗原将成为目标，我们将与CLIA认证的图像细胞计数法合作 实验室开发CMV CISH测定，以表征高级别中CMV的存在和异质性， 神经胶质瘤此外，Core 3将提供高度专业化和全面的分析平台，包括 免疫表型分析、免疫功能分析和TCR测序。我们将利用高维流 流式细胞术，以确定在项目1中抗CD 27治疗后以及随后的治疗后TReg耗竭是否持续 洛莫司汀给药方案3。我们将使用多功能T细胞试验来确定抗CD 27 增加CD 4和CD 8抗原特异性疫苗诱导T细胞的频率和相对多功能性 细胞反应。T细胞免疫应答的评估也将使用相同的高度免疫组织化学方法来测量。 在项目2和项目3中通过该核心进行标准化和验证的测定。

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.