Clinical Immunology Core

临床免疫学核心

• 批准号: 7784223
• 负责人: MARY ELLEN CONLEY
• 金额: $ 35.27万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7784223
• 关键词: Ambulatory Care Facilities; B-Lymphocytes; Biological Assay; Blood; Bone Marrow; Bromodeoxyuridine; Caring; Cell Count; Cell Line; Cell Separation; Cells; Centrifugation; Clinic; Clinical; Clinical Immunology; Clinical Trials; Clonality; Cytokine Signaling; DNA; Development; Diagnosis; Disease; Dose; Enrollment; Evaluation; Excision; Family; Ficoll; Flow Cytometry; Freezing; Funding; Gene Transfer; Hematopoietic; IL2RG gene; Immune; Immune system; Immunology; Infant; Laboratories; Lentivirus Vector; Letters; Life; Long-Term Care; Lymphocyte; Measures; Medical; Mitogens; Molecular Analysis; Mononuclear; Patient Care; Patients; Phytohemagglutinins; Production; Protocols documentation; RNA; Saint Jude Children' s Research Hospital; Sampling; Single-Gene Defect; Site; Stem cell transplant; T-Cell Proliferation; T-Cell Receptor; T-Lymphocyte; Testing; Time; Transplantation; Wiskott-Aldrich Syndrome; cell bank; clinical care; density; expression vector; gene therapy; peripheral blood; pre-clinical; programs; reconstitution; response; transgene expression; uptake; vector

Immunology Core D will provide clinical and laboratory support for the studies in Projects 2 and 3 involving gene transfer for Wiskott Aldrich syndrome (WAS) and SCID-Xl. Preclinical support for these projects will include providing primary T lymphoctyes and EBV-immortalized B cells from WAS and SCID-X1 patients for testing expression and function of lentiviral vectors intended for use in clinical trials. Another function of the Immunology Core is to provide otherwise clinically unavailable assays that are necessary for evaluation of immune reconstitution in treated patients. Specifically, the Core will provide for flow cytometric analysis and cell sorting of peripheral blood and bone marrow hematopoietic cells from treated WAS and SCID-Xl patients. These samples will be used for evaluating lymphocyte reconstitution and development, vector-encoded transgene expression, vector copy number, and integration site analyses. The Core will also provide a T cell proliferation assay that will be used to measure the functional correction of cytokine signaling in cells from SCID-Xl patients. Proliferation responses to varying concentrations of phytohemagglutinin will be determined by BrdU uptake and compared to that seen with normal T cells. The Core will also provide an assay for T cell receptor excision circles (TRECs) as a measure of thymic maturation and ongoing production of post-thymic T cells. This assay will be used to measure T cell reconstitution in the SCID-Xl and WAS clinical gene transfer trials and will provide an important clinical endpoint for these protocols. The Core will also provide an assay for TCRV-beta spectratyping in order to assess T cell diversity and clonality during immune reconstitution. Finally, the Core will provide critical clinical support for Projects 2 and 3 through patient diagnosis, recruitment, treatment, and followup. Dr. Mary Ellen Conley, the Core Leader, oversees an outpatient clinic at St. Jude that provides care for 120 patients with single gene defects of the immune system. This clinic currently includes 20 patients with SCID and 17 patients with WAS. Together with Dr. Leung, Director of Stem Cell Transplantation, Dr. Conley will oversee the clinical care for patients enrolled on our gene transfer protocols.

免疫学核心 D 将为项目 2 和 3 的研究提供临床和实验室支持，涉及 Wiskott Aldrich 综合征 (WAS) 和 SCID-Xl 的基因转移。对这些项目的临床前支持将 包括为 WAS 和 SCID-X1 患者提供原代 T 淋巴细胞和 EBV 永生化 B 细胞 测试用于临床试验的慢病毒载体的表达和功能。的另一个功能是 免疫学核心是提供临床上无法进行的评估所需的测定 治疗患者的免疫重建。具体来说，核心将提供流式细胞术分析和 对来自处理过的 WAS 和 SCID-Xl 的外周血和骨髓造血细胞进行细胞分选 患者。这些样本将用于评估淋巴细胞的重建和发育，载体编码 转基因表达、载体拷贝数和整合位点分析。核心还将 提供 T 细胞增殖测定，用于测量细胞因子信号转导的功能校正 来自 SCID-X1 患者的细胞。对不同浓度植物血凝素的增殖反应将 通过 BrdU 摄取来确定，并与正常 T 细胞所观察到的进行比较。核心还将提供一个 T 细胞受体切除环 (TREC) 测定作为胸腺成熟和持续的测量 胸腺后 T 细胞的产生。该测定将用于测量 SCID-Xl 中的 T 细胞重建 和 WAS 临床基因转移试验将为这些方案提供重要的临床终点。这 Core 还将提供 TCRV-β 谱型分析方法，以评估 T 细胞多样性和克隆性 在免疫重建过程中。最后，核心将为项目 2 和 3 提供关键的临床支持 通过患者诊断、招募、治疗和随访。核心领导人玛丽·艾伦·康利博士， 监督圣裘德的一家门诊诊所，该诊所为 120 名患有单基因缺陷的患者提供护理 免疫系统。该诊所目前有 20 名 SCID 患者和 17 名 WAS 患者。一起 康利博士将与干细胞移植主任梁博士一起监督患者的临床护理 注册了我们的基因转移协议。