Modulating T-cell costimulation as new immunosuppressive concept in organ transplantation

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.