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.

项目概要系统性硬化症 (SSc) 是一种系统性自身免疫性疾病，会导致皮肤和皮肤广泛纤维化内脏、血管脱落和自身抗体形成。 SSc 的病死率是所有国家中最高的系统性自身免疫性疾病，尚有 FDA 批准的治疗方法。基因表达数据分析从 SSc 患者收集的样本强烈表明替代激活的巨噬细胞是关键 SSc 发病机制的驱动因素。我们的目标是开发一种细胞疗法，通过使用替代激活的巨噬细胞嵌合抗原受体（CAR）。除了激活巨噬细胞消除之外，我们还将设计构建体能够分泌抗纤维化分子来逆转甚至改善局部纤维化过程并可能具有系统性。在第一阶段结束时，我们将选择一个先导构建体（基于体内读数）用于第二阶段的 IND 支持研究。