Immunosuppression in Transplantation

The field of soLid organ transplantation has rapidly evolved into the treatment of choice for many end-stage organ illnesses. Much of this evolution is attributable to significantly improved short-term outcomes resulting from successful immunosuppressive therapies and a reduction in acute rejection rates. However, long-term transplant outcomes adversely affected by toxicities associated with standard immunosuppressive agents remain an area for improvement. Thus, recent immunosuppressive strategies have trended toward the development of more selective, targeted therapeutics with less off-target toxicities and away from nonselective agents with burdensome systemic effects that adversely affect long-term patient and graft survivals. This article reviews the mechanisms of action, adverse effects, and cLinical uses of current immunosuppressive agents. It highLights the transition from nonspecific drugs Like steroids and azathioprine to highly engineered and rationally developed protein-based therapeutics such as the costimulation blocker belatacept. Advances in the field along with the need for improved long-term outcomes have faciLitated introduction of biologic, T cell-specific protein therapeutics, but much more remains to be achieved with regard to control of the B cell and alloantibody responses and overcoming the development barriers of a risk-averse pharmaceutical environment.

Duke Scholars

Author Stuart Johnston Knechtle Surgery, Abdominal Transplant Surgery