Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Drugs. 2020 Jan;80(1):33-46. doi: 10.1007/s40265-019-01226-6.
Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success. Belatacept, an immunosuppressive drug that selectively targets the CD28-CD80/CD86 pathway, is the only costimulation blockade therapy that is currently approved for kidney transplant recipients. In the last decade, belatacept therapy has been shown to be a promising therapy in subgroups of kidney transplant recipients; however, the widespread use of belatacept has been tempered by an increased risk of acute kidney transplant rejection. The purpose of this review is to provide an overview of the costimulation blockade therapies that are currently in use or being developed for kidney transplant indications.
T 细胞与抗原呈递细胞之间的共刺激对于调节有效的同种免疫反应至关重要,而这一过程不能通过肾移植后的常规免疫抑制疗法来实现。生物制剂的共刺激阻断疗法可以精确靶向免疫反应,而不会产生非免疫不良事件。已经开发出多种共刺激阻断方法,这些方法在不同程度上抑制了肾移植受者的同种免疫反应。巴利昔单抗是一种免疫抑制剂,可选择性靶向 CD28-CD80/CD86 通路,是目前唯一批准用于肾移植受者的共刺激阻断疗法。在过去十年中,巴利昔单抗治疗已被证明在某些亚组肾移植受者中具有良好的疗效;然而,巴利昔单抗的广泛应用受到急性肾移植排斥风险增加的限制。本文旨在概述目前用于肾移植适应证或正在开发的共刺激阻断疗法。