Combination cell therapy for immunomodulation in kidney transplantation

Transplantation is the best treatment for eligible patients with terminal chronic kidney failure. Despite substantial progress over the last decades, long-term outcome after kidney transplantation remains suboptimal, in large part due to the continuous immune response against the transplanted organ, which needs to be reduced by immunosuppressive drugs that are only partially effective and have side effects. Various cell therapies are currently being evaluated with the aim to reduce or eliminate immunosuppressive drug therapy after transplantation. In preclinical research we could show that combining therapy with regulatory T cells (Tregs, a lymphocyte population that downregulates immune responses) with donor bone marrow transplantation leads to chimerism and tolerance with a minimally toxic treatment protocol.

In this project we conducted an early phase clinical trial which tested for the first time this new treatment combining two types of cell therapy for kidney transplant recipients. As planned, 12 patients were enrolled in the trial. T cell-mediated rejection episodes occurred in 3 patients, which could be treated well, but no antibody-mediated rejection (a severer form of rejection) was observed. Overall, the study group showed good function of the transplanted kidney. Immunosuppressive drugs could be minimized in 3 of 6 patients so far. Donor leukocyte chimerism, a sign that the bone marrow transplant was successful, was detectable in all patients of the study group for a short period after transplantation. Several laboratory assays suggest that the combined cell therapy had a positive effect on the recipients’ immune system, reducing its reactivity against the donor kidney. The encouraging results of this pilot trial demonstrate that the tested combined cell therapy is a promising new treatment that should be explored in further trials. It is hoped that this new approach will eventually help to improve long-term outcome after kidney transplantation.