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.

项目摘要/摘要 我们开发了管理免疫治疗酶的创新新方法 这可以坚固地将免疫细胞从慢性炎症转移到稳态。 代谢编程。在组织锚和 研究了循环形式，量化了作用的细胞机制，以确定 如果不同的管理路线提供优势。需要新的治疗性 慢性自身炎症性疾病，牛皮癣的选择，不可逆转地损害表皮 组织。