Cellular Immunotherapy for SSc

SSc 的细胞免疫治疗

基本信息

批准号：
9465740
负责人：
Joana M Murad
金额：
$ 22.5万
依托单位：
CELDARA MEDICAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-07 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9465740
关键词：
Antigen Targeting Antigens Attenuated Autoantibodies Autoimmune Diseases Biological Markers Bleomycin Blood Vessels Case Fatality Rates Cells Data Defect Development Disease Disease Progression Dropout Environment Environmental Risk Factor Enzymes Evaluation FDA approved Fibrosis Gene Expression Gene Expression Profiling Genetic Genetic Predisposition to Disease Goals Grx1 protein Immune response Immunologic Surveillance Immunotherapy In Vitro Individual Inflammatory Innate Immune System Interferon Type II Killer Cells Lead Link Lymphocyte Malignant Neoplasms Mediating Medical Modeling Molecular Mycoses Organ Pathogenesis Pathology Pathway Analysis Pathway interactions Patients Phase Plant Roots Process Production Pulmonary Fibrosis Research Sampling Signal Transduction Small Business Innovation Research Grant Specificity System Systemic Scleroderma T-Lymphocyte Testing Tissues Transforming Growth Factor beta Virus Diseases Work base cellular transduction chimeric antigen receptor cohort cytokine cytotoxic cytotoxicity design design and construction disease heterogeneity efficacy evaluation experimental study genome-wide analysis in vivo in vivo Model innovation insight macrophage mouse model novel novel strategies novel therapeutics phase 2 study skin fibrosis systemic autoimmune disease systemic toxicity vector control

项目摘要

Project Summary Systemic sclerosis (SSc) is a systemic autoimmune disease that results in widespread fibrosis of the skin and internal organs, vascular dropout and autoantibody formation. SSc has the highest case fatality rate of any systemic autoimmune disease and there remain for FDA approved therapies. Analysis of gene expression data on samples collected from SSc patients strongly indicates that alternatively activated macrophages are the key drivers of SSc pathogenesis. Our goal is to develop a cellular therapy that will target alternatively activated macrophages through the use of a chimeric antigen receptor (CAR). In addition to activated macrophage elimination, we will design constructs that will be capable of secreting antifibrotic molecules to revert or even ameliorate the fibrotic process locally and potentially systemically. At the end of Phase I, we will have selected a lead construct (based on in vivo readouts) for IND-enabling studies in Phase II.

项目摘要全身性硬化症（SSC）是一种全身性自身免疫性疾病，可导致皮肤和内部器官，血管辍学和自身抗体形成。 SSC的病例死亡率最高全身性自身免疫性疾病以及FDA批准的疗法仍然存在。基因表达数据的分析在从SSC患者那里收集的样品上，强烈表明替代激活的巨噬细胞是关键 SSC发病机理的驱动因素。我们的目标是开发一种细胞疗法，该疗法将通过使用嵌合抗原受体（CAR）。除了激活的巨噬细胞消除外，我们还将设计构造这将能够分泌抗纤维化分子以恢复甚至改善本地的纤维化过程并可能系统地。在第一阶段结束时，我们将选择一个铅构建体（基于体内读数）用于II阶段的辅助研究。