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 相关研究和免疫监控核心（核心3）将为完成这三个项目提供 计划项目赠款提案综合，最先进的生物座和免疫/分子概况 一支高度成就的研究科学家团队的支持，他们利用了这些特定平台 与先前和/或当前癌症免疫疗法试验的结合。这三个项目调查了 新型免疫治疗方法治疗患者的安全，效率和机制 胶质母细胞瘤（GBM），一种诊断，预后极不良。该核心的目标是确定 免疫相关性，可预测临床结果并利用A提供机械见解 高度标准化和/或正式验证的测定平台的全面曲目。这个核心也将 提供与生物统计学合作的免疫/分子分析领导和专业知识 生物信息学核心（核心1）以及所有项目的临床试验和成像核心（核心2）。这是至关重要的 拟议的项目旨在定义明确，准确诊断出高级神经胶质瘤，这将是 由此核心提供。拟议项目所需的高质量血液和组织样本将是 由这个核心交付。该建议中的组织病理学服务包括表征肿瘤内 通过组织差异良好的和高级浸润的星形胶质瘤的异质性 根据需要，诊断和分级以及对人神经胶质瘤组织中抗原表达的体外分析。这 GBM中的CMV PP65抗原将成为目标，我们将与CLIA认证的图像细胞仪合作 实验室开发CMV CISH分析，以表征高级CMV的存在和异质性 神经胶质瘤。此外，核心3将提供高度专业化和全面的测定平台，包括 免疫表型，免疫功能分析和TCR测序。我们将利用高维流量 细胞仪确定在项目1中抗CD27治疗后是否持续treg耗竭并随后持续 项目3中的Lomustine给药。我们将使用多功能T细胞测定法确定抗CD27是否 增加CD4和CD8抗原特异性疫苗诱导的T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测量 该核心在项目2和项目3中通过该核心进行了标准化和验证的测定。