Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients
Résumé
Short-term outcomes in kidney transplantation are marred by progressive transplant
failure and mortality secondary to immunosuppression toxicity. Immune modulation
with autologous polyclonal regulatory T cell (Treg) therapy may facilitate immunosup-
pression reduction promoting better long-term clinical outcomes. In a Phase I clini-
cal trial, 12 kidney transplant recipients received 1–10 × 106 Treg per kg at Day +5
posttransplantation in lieu of induction immunosuppression (Treg Therapy cohort).
Nineteen patients received standard immunosuppression (Reference cohort). Primary
outcomes were rejection-free and patient survival. Patient and transplant survival was
100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in the
reference cohort at 48 months posttransplant. Treg therapy revealed no excess safety
concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil with -
drawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted in
a long-lasting dose-dependent increase in peripheral blood Tregs together with an
increase in marginal zone B cell numbers. We identified a pretransplantation immune
phenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. Autologous
Treg therapy is feasible, safe, and is potentially associated with a lower rejection rate
than standard immunosuppression. Treg therapy may provide an exciting opportunity
to minimize immunosuppression therapy and improve long-term outcomes
Domaines
Médecine humaine et pathologie
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