Tissue-Targeted Enzyme for Localized Tryptophan Catabolism to Direct Subcutaneous and Oral Mucosal Inflammatory Responses

用于局部色氨酸分解代谢的组织靶向酶以指导皮下和口腔粘膜炎症反应

• 批准号: 9403768
• 负责人: Benjamin George Keselowsky
• 金额: $ 56.78万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9403768
• 关键词: Affinity; Animal Tarsus; Apoptosis; Area; Autoimmunity; Avidity; Binding; Bone Resorption; Carbohydrates; Catabolism; Cell physiology; Cellular Metabolic Process; Chimera organism; Chimeric Proteins; Chronic; Consumption; Data; Dioxygenases; Disease; Environment; Enzymes; Essential Amino Acids; Extracellular Matrix; Family; Galectin 3; Goals; Homeostasis; Immune; Immune system; Immunosuppressive Agents; Immunotherapy; In Vitro; Individual; Inflammation; Inflammatory; Inflammatory Response; Investigation; Kynurenine; Lectin; Leukocytes; Lipopolysaccharides; Luciferases; Maintenance; Mediating; Metabolic; Modeling; Oral; Oral mucous membrane structure; Osteoclasts; Pathway interactions; Peptides; Periodontal Diseases; Pregnancy; Process; Production; Regulatory T-Lymphocyte; Surface; T cell anergy; T cell response; T-Lymphocyte; Technology; Time; Tissues; Tooth Loss; Transplantation; Treatment Efficacy; Tryptophan; Tryptophan Metabolism Pathway; cancer therapy; carbohydrate binding protein; design; efficacy testing; in vivo; indoleamine; innovation; lactosamine; member; novel strategies; overexpression; programs; response; self assembly; soft tissue; subcutaneous

Project Summary/Abstract There is a considerable need for targeted technologies that direct the immune system for the controlled suppression of localized inflammation. Programming immune cell metabolism is a new and active area of investigation with numerous diverse immunotherapy applications. We are developing an innovative new approach of locally administering a tissue-targeted chimeric enzyme which catabolize the essential amino acid, tryptophan, and produces kynurenines, together inducing a powerful immunosuppressive metabolic programming. The chosen tissue targeting domain confers prolonged tissue retention, and the enzymatic activity can block local inflammation for an extended time. We are applying this technology for the amelioration of periodontal disease, in which localized non-resolving chronic inflammation is associated with a shift away from a submucosal environment rich in tolerance toward one of inflammation consisting of Th1 and Th17 T cells at the expense of regulatory T cells.

项目概要/摘要 非常需要有针对性的技术来指导免疫系统 局部炎症的受控抑制。编程免疫细胞代谢是一种新的 以及具有众多不同免疫治疗应用的活跃研究领域。我们是 开发一种局部施用组织靶向嵌合体的创新方法 分解代谢必需氨基酸色氨酸并产生犬尿氨酸的酶， 共同诱导强大的免疫抑制代谢程序。所选组织 靶向结构域可延长组织保留时间，并且酶活性可以阻断局部 炎症时间较长。我们正在应用这项技术来改善 牙周病，其中局部不可解决的慢性炎症与牙周病有关 从富含耐受性的粘膜下环境转向由炎症组成的一种环境 Th1 和 Th17 T 细胞以牺牲调节性 T 细胞为代价。