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.

项目总结/文摘