Precision medicine guided development of new immunosuppression strategies in solid organ transplantation

Corticosteroids, calcineurin inhibitors, antimetabolites, and mammalian target of rapamycin (mTOR) inhibitors have formed the basis of immunosuppression in clinical solid organ transplantation for decades. This review aims to outline recent advances in precision-based immunosuppression for solid organ transplantation.

Co-stimulation blockade has been explored as both tolerogenic and maintenance immunosuppression over the last two decades, resulting in the application of belatacept in clinical settings. Dual co-stimulation blockade is the latest in this area of study. Recent updates in monoclonal antibody-based immunotherapy have resulted in widespread off-label clinical implementation of eculizumab and alemtuzumab with new drugs still in phase II/II trials. Additional strategies, including autologous regulatory T cell (Treg) and chimeric antigen receptor-Treg cell (CAR-Treg) based therapies, are at the forefront of therapeutic immunomodulation. Early data have demonstrated safety and feasibility with ongoing phase II studies in these cell-based therapies, aiming to verify efficacy in early and long-term graft survival.

The past decade has seen advancement in costimulatory blockade, as well as immune modulatory therapy with monoclonal antibodies. Cellular therapies such as CAR-Tregs remain in the early clinical trial phase.