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和项目3中涉及的研究提供临床和实验室支持