Next-generation regulatory T-cell therapy to battle transplant rejection

The long-term benefits of organ transplantation are hindered by graft rejection, a detrimental process driven by alloreactive T cells. Regulatory T cells (Tregs) are immunosuppressive T cells with a fundamental role in the maintenance of tolerance. Currently, clinical trials at KHP are assessing the safety of polyclonal Tregs in kidney and liver transplanted recipients. Importantly, we and others demonstrated that genetically-engineered donor-specific Tregs are superior to polyclonal Tregs at reducing graft rejection. Chimeric antigen receptors (CARs) are synthetic fusion molecules that translate the binding of specific antigens into delivery of a tailored signal and confer donor-specificity to Tregs. Currently, there is a lack of in vivo information on their whereabouts, longevity, and precise mechanism of action. Rendering CAR Tregs traceable in vivo is urgently required for the translation of this most promising therapy.