Serra Pau, Santamaria Pere
Institut D'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Front Immunol. 2021 Jan 26;11:621774. doi: 10.3389/fimmu.2020.621774. eCollection 2020.
The development of autoimmunity results from a breakdown of immunoregulation and involves cellularly complex immune responses against broad repertoires of epitope specificities. As a result, selective targeting of specific effector autoreactive T- or B-cells is not a realistic therapeutic option for most autoimmune diseases. Induction of autoantigen-specific regulatory T-cells capable of effecting bystander (dominant), yet tissue-specific, immunoregulation has thus emerged as a preferred therapeutic alternative. We have shown that peptide-major histocompatibility complex (pMHC)-based nanomedicines can re-program cognate autoantigen-experienced T-cells into disease-suppressing regulatory T-cells, which in turn elicit the formation of complex regulatory cell networks capable of comprehensively suppressing organ-specific autoimmunity without impairing normal immunity. Here, we summarize the various pMHC-based nanomedicines and disease models tested to date, the engineering principles underpinning the pharmacodynamic and therapeutic potency of these compounds, and the underlying mechanisms of action.
自身免疫的发展源于免疫调节的崩溃，涉及针对广泛表位特异性的细胞复杂免疫反应。因此，对于大多数自身免疫性疾病而言，选择性靶向特定效应自身反应性T细胞或B细胞并非现实的治疗选择。能够实现旁观者（显性）但组织特异性免疫调节的自身抗原特异性调节性T细胞的诱导，已成为一种首选的治疗替代方案。我们已经表明，基于肽-主要组织相容性复合体（pMHC）的纳米药物可以将同源自身抗原经历的T细胞重新编程为疾病抑制性调节性T细胞，进而引发能够全面抑制器官特异性自身免疫而不损害正常免疫的复杂调节细胞网络的形成。在此，我们总结了迄今为止测试的各种基于pMHC的纳米药物和疾病模型、支撑这些化合物药效学和治疗效力的工程原理以及潜在的作用机制。
