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University of Pennsylvania Clinical Autoimmunity Center of Excellence

宾夕法尼亚大学临床自身免疫卓越中心

基本信息

批准号：
9918249
负责人：
AMIT BAR-OR
金额：
$ 7.89万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9918249
关键词：
Address Antigen Targeting Antigens Autoantigens Autoimmune Diseases Autoimmune Process Autoimmunity Automobile Driving B-Lymphocyte Subsets B-Lymphocytes Biological Biological Markers Blood Brain Cellular immunotherapy Chronic Clinical Clinical Research Clinical Trials Clone Cells Communication Communication Programs Development Disease Disease remission Dose Engineered Gene Epigenetic Process Fellowship Fostering Functional disorder Funding Future Future Generations Goals Grant Review Human Immune Immune Tolerance Individual Infection Inflammatory Infrastructure Institution Insulin-Dependent Diabetes Mellitus Islet Cell Knowledge Lead Life Magnetic Resonance Imaging Maintenance Mediating Mentors MicroRNAs Mucous Membrane Multiple Sclerosis Myelogenous Pancreas Pancreatic Injury Patients Pemphigus Vulgaris Pennsylvania Peripheral Phase Phenotype Physicians Placebos Population Randomized Randomized Clinical Trials Research Risk Safety Scientist T-Lymphocyte T-Lymphocyte Subsets Time Tissue imaging Tissues Translational Research Travel Treatment Protocols Universities Withdrawal Work anti-CD20 base career career development clinical care commensal microbes effective therapy first-in-human innovation insight multiple sclerosis patient next generation novel novel therapeutics open label patient subsets potential biomarker predictive marker programs prospective randomized trial secondary lymphoid organ standard of care transcriptome transcriptome sequencing transcriptomics translational research program translational study treatment effect treatment strategy

项目摘要

The overall goals of the University of Pennsylvania Clinical Autoimmunity Center of Excellence (Penn ACE) are 1) to perform cutting-edge clinical and translational research to advance our understanding of human autoimmunity through Clinical and Collaborative Projects, 2) to encourage the next generation of physician- scientists to pursue clinical and translational research in autoimmunity through Scientific Communications and Mentoring and Enrichment Programs overseen by an Administrative Core, and 3) to provide the financial and regulatory guidance and infrastructure to support collaborative scientific interactions within and between academic institutions nationwide through an ACE Funds Management Core. The clinical and translational research program of the Penn ACE centers around the theme of “B cells as drivers of autoimmunity”, focusing on three debilitating and potentially life-threatening autoimmune diseases (pemphigus vulgaris (PV), multiple sclerosis (MS), and type 1 diabetes (T1D)) for which prospective randomized clinical trials of anti-CD20-mediated B cell depletion have demonstrated significant clinical benefit. Thus, B cells are key drivers of autoimmunity in these conditions, but risk of serious and potentially fatal infections compromises the utility of chronic B cell depletion as a long-term treatment strategy. Each of the proposed Clinical and Collaborative Projects, as well as the Administrative Core, addresses a key question or barrier to progress in the field. The Primary Clinical Project will execute a phase 1b open-label dose escalation study to evaluate the safety, tolerability, and potential efficacy of a novel gene-engineered cellular immunotherapy known as DSG3-CAART to achieve targeted, antigen-specific B cell depletion and lasting disease remission in PV. The Alternate Clinical Project will utilize a prospective randomized trial of ocrelizumab withdrawal in MS to evaluate whether B cell depletion can be safely withdrawn in MS patients without compromising efficacy and will identify potential biomarkers that predict long-term tolerance induction. A Collaborative Project will perform deep phenotyping, immune repertoire analysis, and target antigen discovery for expanded B cell clones in the pancreas, secondary lymphoid organs, and blood of patients with T1D, which may not only identify novel therapeutic strategies for T1D, but also establish a framework for how similar experimental approaches can be used to elucidate the pathophysiology and targets of B cells in a broad range of other autoimmune diseases. Finally, an Administrative Core will implement a scientific communications and mentoring program to foster collaborative research within and beyond the Penn ACE and encourage future generations of physician-scientists to pursue careers in autoimmune disease clinical care and research.

宾夕法尼亚大学临床自身免疫卓越中心的总体目标是