Emerging immunomodulatory therapies targeting the co-stimulatory pathways for the prevention of transplant rejection.

The continued discovery of novel immune molecules and pathways over the last decade has spurred a tremendous amount of research into the targeting of these pathways for the prevention of transplant rejection. Of particular interest are members of the ever-growing family of T-cell co-stimulatory pathways; the classic co-stimulatory pathways are the CD28/CTLA4:B7-1/2 and CD40:CD154, while the ICOS:ICOSL and PD-1:PD-L1/PD-L2 pathways are novel. Various chimeric molecules and monoclonal antibodies have been developed for targeting these pathways with promising results, especially with the newer generation of agents and in combination among themselves, with other immunomodulatory therapies and/or with conventional immunosuppressive agents. These novel immunomodulatory strategies have the potential to bring us a step closer to achieving transplantation tolerance.