Center of Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, Australia.
Faculty of Medicine and Health, Sydney Medical School, University of Sydney, Sydney, Australia.
Transplantation. 2021 Dec 1;105(12):e303-e321. doi: 10.1097/TP.0000000000003765.
Transplantation is now performed globally as a routine procedure. However, the increased demand for donor organs and consequent expansion of donor criteria has created an imperative to maximize the quality of these gains. The goal is to balance preservation of allograft function against patient quality-of-life, despite exposure to long-term immunosuppression. Elimination of immunosuppressive therapy to avoid drug toxicity, with concurrent acceptance of the allograft-so-called operational tolerance-has proven elusive. The lack of recent advances in immunomodulatory drug development, together with advances in immunotherapy in oncology, has prompted interest in cell-based therapies to control the alloimmune response. Extensive experimental work in animals has characterized regulatory immune cell populations that can induce and maintain tolerance, demonstrating that their adoptive transfer can promote donor-specific tolerance. An extension of this large body of work has resulted in protocols for manufacture, as well as early-phase safety and feasibility trials for many regulatory cell types. Despite the excitement generated by early clinical trials in autoimmune diseases and organ transplantation, there is as yet no clinically validated, approved regulatory cell therapy for transplantation. In this review, we summarize recent advances in this field, with a focus on myeloid and mesenchymal cell therapies, including current understanding of the mechanisms of action of regulatory immune cells, and clinical trials in organ transplantation using these cells as therapeutics.
移植现在已经在全球范围内作为常规程序进行。然而，对供体器官的需求增加以及随之而来的供体标准的扩大，使得最大限度地提高这些器官质量成为当务之急。目标是平衡保存移植物功能与患者的生活质量，尽管要长期接受免疫抑制治疗。为避免药物毒性而消除免疫抑制疗法，同时接受所谓的“免疫耐受”的同种异体移植物，事实证明这是难以实现的。免疫调节药物开发方面缺乏近期进展，加上肿瘤免疫治疗方面的进展，促使人们对细胞为基础的疗法产生了兴趣，以期控制同种异体免疫反应。大量的动物实验工作已经确定了可以诱导和维持耐受的调节性免疫细胞群体，证明它们的过继转移可以促进供体特异性耐受。这项广泛的工作延伸出了许多调节性细胞类型的制造方案，以及早期安全性和可行性临床试验。尽管早期在自身免疫性疾病和器官移植方面的临床试验令人兴奋，但目前还没有经过临床验证和批准的用于移植的调节性细胞疗法。在这篇综述中，我们总结了该领域的最新进展，重点介绍了髓系和间充质细胞疗法，包括对调节性免疫细胞作用机制的现有理解，以及使用这些细胞作为治疗剂的器官移植临床试验。
