Current state of organ transplant tolerance

Immunological tolerance has long been considered the 'holy grail' of organ transplantation. Although tolerance has been an active area of research for 70 years, its clinical application has only been possible in the last two decades and widespread use remains an, as yet, unattained goal. Recent advances in the understanding of immune regulation have identified many new approaches to tolerance induction and several clinical trials are currently aimed at bringing this treatment to more patients.

Mixed chimerism remains the most successful approach to tolerance induction. However, many treatments, including adoptive transfer of regulatory T cells, regulatory B cells, and immune suppressive dendritic cells and myeloid derived suppressor cells have shown great promise in preclinical models. Recent clinical studies have found that both kidney and liver operational tolerance are achievable in the appropriate settings. Furthermore, combining multiple tolerance approaches has shown potential to produce durable and safer tolerance.

Tolerance to protect kidney and liver allografts has become a valuable therapy in the correct circumstances. Through further clinical trials and an improved understanding of immune regulatory components, tolerance is poised to have a significant impact on transplantation in the years to come.