History of organ transplantation and the development of key immunosuppressants

ABSTRACT

The history of organ transplantation is limited to the last century. To overcome the barrier of the host immune system, which results in transplant rejection, the pioneers of transplantation achieved their first success by performing a kidney transplantation between identical twins. This achievement led the transplant clinicians to perform transplantations with immunological barriers present. Strategies such as whole-body irradiation combined with steroids yielded success in kidney transplantation between non-identical twins and siblings. However, owing to the toxicity related to irradiation, the paradigm shifted to the use of immunosuppressants. Azathioprine, steroids, and anti-lymphocyte globulin became the first multiple immunosuppressive regimens. With the introduction of cyclosporine, the 1-year survival rate increased by more than 80%. Cyclosporine, azathioprine, and steroids became the new standard maintenance regimens until the introduction of tacrolimus and mycophenolate mofetil, which replaced cyclosporine and azathioprine, respectively. The most recent change in immunosuppressants was the development of monoclonal antibodies with specific binding sites, such as CD20 (rituximab) and CD25 (basiliximab). With the innovation of molecular engineering and new insights into the costimulatory pathways, new molecules are under investigation in the field of transplantation.