Conclusion

Abstract

In light of the recent demonstration that intragraft mechanisms appear to be important in regulating virtually all phases of the rejection response, and that local immunosuppression achieves the goals of preventing rejection with reduced systemic drug exposure and toxicity in rodent and canine models, it is clear that the concept deserves continued exploration and eventual clinical application. Pharmaceutical companies must become interested in the development of immunosuppressant prodrugs that are selectively activated in and then rapidly eliminated by the transplanted organ of interest or the systemic circulation, and in the development of active agents that are pharmacokinetically tailored for pump-based local administration to a given target organ. New methods of local drug delivery, such as nanoparticle and magnetically-localized therapeutic carriers, should be applied to organ transplantation. Finally, research efforts must be continued towards the goal of utilizing gene transfer techniques to obtain stable, long-term local immunosuppression of immediately-vascularized solid-organ transplants in large animals and man.