Correlative Studies and Immune Monitoring Core

相关研究和免疫监测核心

• 批准号: 10477346
• 负责人: Kent J. Weinhold
• 金额: $ 22.02万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10477346
• 关键词: Antibody Therapy; Antigens; Applications Grants; Astrocytoma; Bioinformatics; Biological Assay; Biometry; Blood; Blood specimen; Brain Neoplasms; CCL3 gene; CD4 Antigens; CD8 Antigens; CLIA certified; Cellular Assay; Clinical; Clinical Research; Clinical Trials; Collaborations; Correlative Study; Cytomegalovirus; Data; Diagnosis; Diphtheria Toxoid; Drug or chemical Tissue Distribution; ERBB2 gene; Enrollment; Epidermal Growth Factor Receptor; Flow Cytometry; Frequencies; Glioblastoma; Glioma; Goals; Heterogeneity; Human; Image Cytometry; Immune; Immune response; Immunologic Monitoring; Immunologics; Immunophenotyping; Immunotherapeutic agent; Immunotherapy; In Vitro; Inflammatory; Infusion procedures; Investigational Therapies; Laboratories; Lead; Leadership; Lomustine; Malignant neoplasm of brain; Measurement; Measures; Molecular Profiling; Monoclonal Antibodies; Oncolytic poliovirus; Outcome; Participant; Pathologic; Patients; Peptides; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Prognosis; Program Research Project Grants; RNA; Recording of previous events; Regulatory T-Lymphocyte; Research; Research Project Grants; Resources; Safety; Sampling; Scientist; Services; Stains; Standardization; T cell receptor repertoire sequencing; T cell response; T-Cell Receptor; T-Lymphocyte; Technology; Testing; Tetanus; Tissue Banks; Tissue Procurements; Tissue Sample; Tissues; Vaccines; accurate diagnosis; anti-tumor immune response; base; biobank; cancer immunotherapy; clinical imaging; cytokine; cytomegalovirus matrix protein 65kDa; effective therapy; experience; high dimensionality; immune function; immunotherapy trials; improved; insight; monocyte; multiplex assay; novel; patient prognosis; peripheral blood; preconditioning; predict clinical outcome; programs; survivin; tool; tumor; tumor heterogeneity; vaccine immunotherapy; vaccine response

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.

项目摘要 – 核心 3 相关研究和免疫监测核心（核心 3）将提供组成此项目的所有三个项目 计划项目拨款提案全面、最先进的生物样本库和免疫/分子分析 由一群卓有成就的研究科学家提供支持，他们利用了这些特定平台 这三个项目与之前和/或当前的癌症免疫治疗试验相结合。 新型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，本核心的目标是识别。 免疫学相关性可预测临床结果并利用 该核心还将提供全面的高度标准化和/或正式验证的检测平台。 与生物统计学和生物统计学合作，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）以及临床试验和成像核心（核心 2）。 拟议的项目旨在明确定义、准确诊断高级别神经胶质瘤，这项服务将 该核心将提供拟议项目所需的高质量血液和组织样本。 该提案中的组织病理学服务包括表征肿瘤内。 组织中分化良好和高级别浸润性星形细胞瘤的异质性 根据需要对人胶质瘤组织中的抗原表达进行诊断和分级以及体外分析。 GBM 中的 CMV pp65 抗原将成为目标，我们将与 CLIA 认证的图像细胞术合作 实验室开发 CMV CISH 测定来表征高级别 CMV 的存在和异质性 此外，Core 3 将提供高度专业化和全面的检测平台，包括 我们将利用高维流进行免疫表型分析、免疫功能分析和 TCR 测序。 细胞计数以确定项目 1 及后续项目中抗 CD27 治疗后 TReg 耗竭是否持续 项目 3 中的洛莫司汀给药。我们将使用多功能 T 细胞测定来确定抗 CD27 是否 增加 CD4 和 CD8 抗原特异性、疫苗诱导 T 的频率和相对多功能性 T 细胞免疫反应的评估也将使用相同的高度进行测量。 项目 2 和项目 3 中该核心的标准化和验证化验。