Tissue-Targeted Drug Delivery Strategies to Promote Antigen-Specific Immune Tolerance.
Tissue-Targeted Drug Delivery Strategies to Promote Antigen-Specific Immune Tolerance.
复制标题
促进抗原特异性免疫耐受的组织靶向药物递送策略。
DOI：
10.1002/adhm.202202238
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发表时间：
2023
影响因子：
10
通讯作者：
Jewell,ChristopherM
中科院分区：
文献类型：
--
作者：
Rui,Yuan;Eppler,HaleighB;Yanes,AlexisA;Jewell,ChristopherM
在自身免疫或器官移植排斥反应期间，免疫系统攻击宿主或移植组织，导致数百万患者的衰弱性炎症。这些疾病中的大多数都无法治愈。此外，现有的治疗方法通过非特异性途径调节炎症，减轻症状，但也损害了患者产生健康免疫反应的能力。最近的临床前进展，以调节免疫功能障碍与疫苗样抗原特异性揭示了令人兴奋的机会，以解决自身免疫性疾病和移植排斥的根本原因。其中几种疗法目前正在进行临床试验，强调了抗原特异性耐受的前景。实现抗原特异性耐受需要精确性，并且通常需要抗原、细胞因子、小分子药物和其他免疫调节剂的组合递送。这可以通过生物材料技术来促进，生物材料技术可以被设计为定向和显示免疫学线索，防止降解，并选择性地将信号传递到特定的组织或细胞群。在这篇综述中，一些关键的免疫细胞群参与自身免疫和健康的免疫耐受。药物输送到免疫器官的机会进行了讨论，其中专门的组织驻留免疫细胞可以被编程为以独特的方式对抗原作出反应。最后，强调了目前正在进行临床试验的基于细胞和生物材料的疗法，以诱导抗原特异性免疫耐受。
During autoimmunity or organ transplant rejection, the immune system attacks host or transplanted tissue, causing debilitating inflammation for millions of patients. There is no cure for most of these diseases. Further, available therapies modulate inflammation through nonspecific pathways, reducing symptoms but also compromising patients’ ability to mount healthy immune responses. Recent preclinical advances to regulate immune dysfunction with vaccine‐like antigen specificity reveal exciting opportunities to address the root cause of autoimmune diseases and transplant rejection. Several of these therapies are currently undergoing clinical trials, underscoring the promise of antigen‐specific tolerance. Achieving antigen‐specific tolerance requires precision and often combinatorial delivery of antigen, cytokines, small molecule drugs, and other immunomodulators. This can be facilitated by biomaterial technologies, which can be engineered to orient and display immunological cues, protect against degradation, and selectively deliver signals to specific tissues or cell populations. In this review, some key immune cell populations involved in autoimmunity and healthy immune tolerance are described. Opportunities for drug delivery to immunological organs are discussed, where specialized tissue‐resident immune cells can be programmed to respond in unique ways toward antigens. Finally, cell‐ and biomaterial‐based therapies to induce antigen‐specific immune tolerance that are currently undergoing clinical trials are highlighted.