Co-signals in organ transplantation

The nonimmune effects of currently used immunosuppressive drugs result in a high incidence of late graft loss due to nephrotoxicity and death. As an immune-specific alternative to conventional immunosuppressants, new biotechnology tools can be used to block the costimulation signal of T-cell activation.

Many experimental studies, particularly preclinical studies in nonhuman primates, have focused on blocking 'classical' B7/CD28 and CD40/CD40L pathways, which are critical in primary T-cell activation, but also on new B7/CD28 and TNF/TNF-R pathways families of costimulatory molecules that can deliver positive or negative costimulation signals to regulate the alloimmune response.

Belatacept is a new fusion protein derived from CTLA4-Ig that can be used to prevent acute rejection in renal transplantation instead of calcineurin inhibitors. Belatacept can also prevent acute rejection efficiently in humans and, more interestingly, can improve renal function and cardiovascular risk factors in this population.