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， 用于Wiskott Aldrich综合征（WAS）和SCID-X1的基因转移。这些项目的临床前支持将 包括提供来自WAS和SCID-X1患者原代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。的另一功能 免疫学核心是提供临床上不可用的检测方法，用于评价 治疗患者的免疫重建。具体而言，核心将提供流式细胞仪分析， 来自经处理的WAS和SCID-X1的外周血和骨髓造血细胞的细胞分选 患者这些样品将用于评价淋巴细胞重建和发育，载体编码 转基因表达、载体拷贝数和整合位点分析。核心也将 提供T细胞增殖测定，其将用于测量细胞因子信号传导的功能校正 在SCID-X1患者的细胞中。对不同浓度的植物血凝素的增殖反应将 可以通过BrdU摄取来确定，并与正常T细胞所见进行比较。核心还将提供一个 T细胞受体切除环（TRECs）测定作为胸腺成熟和持续性胸腺发育的指标 胸腺后T细胞的产生。该测定将用于测量SCID-X1中的T细胞重建。 和WAS临床基因转移试验，并将为这些方案提供重要的临床终点。的 Core还将提供TCRV-β谱分析，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。玛丽艾伦·康利博士，核心领导人 监督圣裘德的一家门诊诊所，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包括20名SCID患者和17名WAS患者。一起 康利医生将与干细胞移植主任梁医生一起监督患者的临床护理 在我们的基因转移方案中登记了