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.

Public Health Relevance

of this Core to the Program Project is that the Immunology Core provides critical expertise necessary for the medical care of patients, the evaluation of patients enrolled on gene transfer protocols in Projects 2 and 3, and the diagnosis and treatment of patient enrolled on these studies. The Core also provides patients samples for molecular analysis and preclinical development.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01HL053749-20
Application #
8716803
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
2014
Total Cost
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
City
Memphis
State
TN
Country
United States
Zip Code
38105
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