Objective

Transplantation has been a very successful approach for the treatment of end stage organ failure. However while immunosuppressive drugs have progressively reduced the incidence of early graft loss, their use has incurred significant costs. Furthermore, current therapies have also failed to prevent chronic allograft dysfunction and the average half-life of solid organ transplants remains approximately 10 years, supporting the need for tolerance induction strategies. One of the successful strategies in preclinical animal models to induce transplantation tolerance has been to expand recipient CD4+CD25+FOXP3+ cells (Tregs) ex vivo and inject them back in vivo. Recently, we have established a GMP compatible protocol for the polyclonal expansion of Tregs and the product has been applied in two clinical trials, the ONE Study and ThRIL, in the treatment of kidney and liver transplant patients, respectively. We have so far treated 18 patients. However, we have demonstrated in preclinical models that Tregs specific for the donor are superior to polyclonal Tregs in prolonging transplant survival. Furthermore, we have started to combine donor-specific Tregs with other strategies such as inhibiting components of the innate immune system to further enhance the strength of Tregs. We believe that these new approaches will inform the future of Treg therapy.