Department of Pathology, University of Pittsburgh Medical Center.
Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh.
Curr Opin Organ Transplant. 2024 Apr 1;29(2):121-130. doi: 10.1097/MOT.0000000000001127. Epub 2023 Nov 22.
Regulatory dendritic cells (DCregs; also 'tolerogenic DCs'), innate immune cells that regulate the alloimmune response, are a novel cellular therapy for organ transplantation. Preliminary results from early-phase clinical trials in live donor kidney and liver transplantation are promising. This follows many years of research elucidating mechanisms of action and utility of DCregs. Herein, we review early-phase clinical trial observations and recent advances in the production, modification, and future-trajectory of DCreg in organ transplantation.
Preclinical work has demonstrated the ability of adoptively transferred DCreg to abrogate ischemia-reperfusion injury and promote long-term allograft survival. Good Manufacturing Practice-grade DCregs have been generated in adequate numbers for early-phase trials of autologous DCregs in kidney transplantation and donor-derived DCreg in liver transplantation. These trials have demonstrated feasibility and safety, with preliminary evidence of an influence on host immune reactivity. In both kidney and liver transplantation, reduced effector CD8 + T-cells have been noted, together with other changes that may be conducive to reduced dependence on immunosuppressive therapy.
Substantial progress has been made in bringing DCreg to clinical testing in organ transplantation. Additional clinical and mechanistic studies are now needed to further explore and garner the full potential of DCreg in organ transplantation.
调节树突状细胞（DCregs；也称为“耐受性树突状细胞”）是一种调节同种免疫反应的固有免疫细胞，是器官移植的一种新型细胞治疗方法。来自活体供肾和肝移植早期临床试验的初步结果令人鼓舞。这是多年来阐明 DCregs 的作用机制和效用的研究成果。本文综述了器官移植中 DCreg 的早期临床试验观察结果和最新进展，包括其生产、修饰以及未来发展方向。
临床前研究已经证明了过继转移的 DCreg 能够减轻缺血再灌注损伤并促进长期同种移植物存活。已经能够以足够数量生成符合良好生产规范（GMP）的 DCregs，用于自体 DCreg 治疗肾移植和供体来源的 DCreg 治疗肝移植的早期临床试验。这些试验已经证明了其可行性和安全性，初步证据表明其对宿主免疫反应有影响。在肾和肝移植中，已观察到效应 CD8+T 细胞减少，同时还发生了其他可能有利于减少对免疫抑制治疗依赖的变化。
在将 DCreg 应用于器官移植的临床测试方面已经取得了实质性进展。现在需要进行更多的临床和机制研究，以进一步探索和充分发挥 DCreg 在器官移植中的潜力。
