Division of Transplantation, Department of Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Curr Opin Organ Transplant. 2012 Aug;17(4):368-75. doi: 10.1097/MOT.0b013e328355fc94.
Blockade of costimulatory signalling is a promising approach to inhibit T-cell responses and consequently allograft rejection. The last decade was marked by progress in understanding the details of various costimulatory pathways and by the development of biologicals targeting these pathways with the aim of selectively and efficiently modulating T-cell responses.
Here we focus on the clinically relevant costimulatory pathways CD28:CD80/86, CD40:CD154 (CD40L), CD2:LFA-3 and ICAM:LFA-1. We will give a short overview of the physiologic function of these pathways and discuss results from preclinical and clinical studies of costimulation blockers targeting these pathways.
The development of costimulation blockers for clinical application in the field of organ transplantation was delayed by several setbacks. However, belatacept has recently been approved as first in class for renal transplantation. Several additional costimulation blockers are under development with some having already entered into clinical trials. Costimulation blockers are a new class of rationally designed immunosuppressive drugs with considerable potential for improving outcome of organ transplantation.
阻断共刺激信号是抑制 T 细胞反应并进而抑制移植物排斥反应的一种很有前途的方法。过去十年，人们对各种共刺激途径的细节有了更深入的了解，并开发了针对这些途径的生物制剂，旨在有选择性和高效地调节 T 细胞反应。
本文主要关注临床相关的共刺激途径 CD28:CD80/86、CD40:CD154（CD40L）、CD2:LFA-3 和 ICAM:LFA-1。我们将简要概述这些途径的生理功能，并讨论针对这些途径的共刺激阻断剂的临床前和临床研究结果。
尽管在器官移植领域，共刺激阻断剂的临床应用因多次挫折而延迟，但贝那普利塞最近已被批准作为治疗肾移植的首创药物。还有一些其他的共刺激阻断剂正在开发中，其中一些已经进入临床试验。共刺激阻断剂是一类经过合理设计的新型免疫抑制剂，具有改善器官移植效果的巨大潜力。
