J Korean Med Assoc.  2020 May;63(5):259-266. 10.5124/jkma.2020.63.5.259.

Future direction of immunosuppressive treatment in organ transplantation

• Park JB

• KMID: 2500712
• DOI: http://doi.org/10.5124/jkma.2020.63.5.259

Abstract

Since the first success of kidney transplantation in 1954, significant advances have been achieved in the field of organ transplantation. It was possible with the introduction of immunosuppressive drugs belonging to the class of calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus, the advances in surgical techniques and perioperative management, the monitoring and management infections, and the highly sensitive and specific antibody detection techniques. Despite recent progress, we currently encounter the limitation of better long-term transplant outcomes mainly because of paradoxical CNI toxicity and failure to control antibody or antibody-mediated rejections. The future direction of immunosuppression can be continued by optimizing immunosuppressive regimens with currently available immunosuppressants for better control of antibodies while avoiding CNI toxicity and by using biological therapeutics such as costimulation blockade agents that provide effective control of antibodies along with a reduction in usage or avoidance of CNIs and may develop as new immunosuppressants in the near future. Moreover, a tolerance induction through transplantation of donor hematopoietic stem cells or an infusion of regulatory cells using various sources of immune cells can also be a promising strategy as it can fundamentally escape from the complications of immunosuppressants. Over and above, it is important to note that the results of clinically applicable immunosuppressants from research in the non-human primate xenotransplantation model at the forefront of the future development of immunosuppressants can be a good opportunity to selectively apply to allo-transplants. No immunosuppressants can be risk-free, and therefore, all new immunosuppressants should be evaluated under the considerations for the risk/benefit ratio in various clinical conditions.

Keyword

Organ transplantation; Immunosuppressive agents; Costimulation blockade; Immune tolerance; Heterologous transplantation