Tissue-Anchored vs. Circulating Engineered Enzyme Constructs for Immunometabolic Resolution of Psoriasis

组织锚定与循环工程酶构建体用于银屑病免疫代谢解决

• 批准号: 10667165
• 负责人: Dorina Avram
• 金额: $ 79.83万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-02 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667165
• 关键词: Address; Anti-Inflammatory Agents; Autoimmune Diseases; Autoimmune Responses; Binding; Biological; Cell physiology; Cells; Chimeric Proteins; Chronic; Circulation; Clinical; Data; Diffusion; Disease; Dose; Engineering; Enzymes; Essential Amino Acids; Galectin 3; Genes; Glycosaminoglycans; Half-Life; Homeostasis; IL17 gene; Imiquimod; Immune; Immune response; Immunocompromised Host; Immunofluorescence Immunologic; Immunosuppression; Immunotherapeutic agent; Impairment; Infection; Inflammation; Inflammatory; Kynurenine; Lymphoid Cell; Maximum Tolerated Dose; Metabolic; Metabolism; Pathogenicity; Pathology; Patients; Pharmaceutical Preparations; Play; Polysaccharides; Predisposition; Production; Psoriasis; Resolution; Role; Route; Skin; Sterility; Stimulus; Therapeutic; Tissues; Toxic effect; Translations; Tryptophan; Tryptophan 2,3 Dioxygenase; Tryptophan Metabolism Pathway; autoinflammatory; autoinflammatory diseases; autosomal dominant mutation; beta-galactoside; carbohydrate binding protein; carbohydrate receptor; cell type; cytokine; enzyme model; extracellular; human model; immune modulating agents; immunoregulation; in vivo; innovation; interleukin-17E; interleukin-22; interleukin-23; keratinocyte; mouse model; novel; novel strategies; novel therapeutics; programs; response; restoration; side effect; success; systemic toxicity; γδ T cells

Project Summary/Abstract We have developed innovative new approaches of administering immunotherapeutic enzymes that robustly directs immune cells away from chronic inflammation toward homeostasis through metabolic programming. Innovative fusion protein enzyme constructs in both tissue-anchored and circulating forms are investigated, quantifying cellular mechanisms of action in order to determine if different administration routes offer advantages. There is considerable need for new therapeutic options for the chronic auto-inflammatory disease, psoriasis, which irreversibly damage epidermal tissues.

项目总结/摘要 我们已经开发出创新的免疫酶管理新方法 它能有力地引导免疫细胞远离慢性炎症， 代谢程序在组织锚定和组织修复中的创新融合蛋白酶构建体 研究循环形式，量化细胞作用机制，以确定 如果不同的给药途径提供优势。对新的治疗方法有相当大的需求。 选择慢性自身炎症性疾病，牛皮癣，这是不可逆的损害表皮 组织中