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

项目摘要/摘要 有相当大的需求有针对性的技术，以指导免疫系统为 对局部炎症有控制的抑制。编程免疫细胞新陈代谢是一种新的 和活跃的研究领域，拥有众多不同的免疫疗法应用。我们是 开发一种局部给药组织靶向嵌合体的创新方法 分解必需氨基酸色氨酸并产生犬尿氨酸的酶， 共同诱导一种强大的免疫抑制代谢程序。选定的组织 靶向结构域可延长组织滞留时间，酶活性可阻断局部 长期发炎。我们正在应用这项技术来改进 牙周病，在这种疾病中，局部的未消退的慢性炎症与 从充满耐受性的粘膜下环境转向由炎症组成的环境 以牺牲调节性T细胞为代价的Th1和Th17T细胞。

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.