Journal article
Feasibility, long‐term safety and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients
- Abstract:
- 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 immunosuppression reduction promoting better long‐term clinical outcomes. In a Phase I clinical trial, 12 kidney transplant recipients received 1‐10x106 Treg per kg at Day+5 post transplantation 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 vs 78.9% in the reference cohort at 48 months post‐transplant. Treg therapy revealed no excess safety concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil withdrawn successfully and remain on tacrolimus monotherapy.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 pre‐transplantation 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.
- Publication status:
- Published
- Peer review status:
- Reviewed (other)
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(Preview, Version of record, pdf, 1.8MB, Terms of use)
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- Publisher copy:
- 10.1111/ajt.16395
Authors
- Publisher:
- Wiley
- Journal:
- American Journal of Transplantation More from this journal
- Volume:
- 21
- Issue:
- 4
- Pages:
- 1603-1611
- Publication date:
- 2020-11-10
- Acceptance date:
- 2020-10-31
- DOI:
- EISSN:
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1600-6143
- ISSN:
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1600-6135
- Pmid:
-
33171020
- Language:
-
English
- Keywords:
- Pubs id:
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1145089
- Local pid:
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pubs:1145089
- Deposit date:
-
2020-11-12
- ARK identifier:
Terms of use
- Copyright holder:
- Harden et al.
- Copyright date:
- 2020
- Rights statement:
- © 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
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