Immunobiology of transplantation: impact on targets for large and small molecules.

Organ transplantation is the preferred method of treatment for many forms of end-stage organ failure. However, immunosuppressive drugs that are used to avoid rejection can result in numerous undesirable effects (infection, malignancy, hypertension, diabetes, and accelerated arteriosclerosis). Moreover, they are not effective at preventing chronic rejection resulting in late graft loss. This review summarizes the fundamental concepts underlying the rejection of solid-organ allografts with the aim of highlighting potential new targets for therapeutics. Future improvement will depend on new therapeutic moieties, including biologics, to target various pathways of both the innate and adaptive arms of immunity. Results from some of the most recent clinical trials in transplantation and emerging new therapies are also discussed.