Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar;103(3):627-637.
doi: 10.1016/j.kint.2022.08.037. Epub 2022 Oct 26.

A Phase I/IIa study of autologous tolerogenic dendritic cells immunotherapy in kidney transplant recipients

Aurélie Moreau  1 , Delphine Kervella  2 , Laurence Bouchet-Delbos  3 , Cécile Braudeau  4 , Soraya Saïagh  5 , Pierrick Guérif  6 , Sophie Limou  3 , Anne Moreau  7 , Sylvain Bercegeay  5 , Mathias Streitz  8 , Birgit Sawitzki  9 , Ben James  10 , Paul N Harden  11 , David Game  12 , Qizhi Tang  13 , James F Markmann  14 , Ian S D Roberts  15 , Edward K Geissler  10 , Brigitte Dréno  5 , Régis Josien  4 , Maria-Cristina Cuturi  3 , Gilles Blancho  16 ; DIVAT consortium
Collaborators, Affiliations

A Phase I/IIa study of autologous tolerogenic dendritic cells immunotherapy in kidney transplant recipients

Aurélie Moreau et al. Kidney Int. 2023 Mar.

Abstract

Kidney transplant survival is shortened by chronic rejection and side effects of standard immunosuppressive drugs. Cell-based immunotherapy with tolerogenic dendritic cells has long been recognized as a promising approach to reduce general immunosuppression. Published trials report the safety and the absence of therapy-related adverse reactions in patients treated with tolerogenic dendritic cells suffering from several inflammatory diseases. Here, we present the first phase I clinical trial results using human autologous tolerogenic dendritic cells (ATDC) in kidney transplantation. Eight patients received ATDC the day before transplantation in conjunction with standard steroids, mycophenolate mofetil and tacrolimus immunosuppression with an option to taper mycophenolate mofetil. ATDC preparations were manufactured in a Good Manufacturing Practice-compliant facility and fulfilled cell count, viability, purity and identity criteria for release. A control group of nine patients received the same standard immunosuppression, except basiliximab induction replaced ATDC therapy and mycophenolate tapering was not allowed. During the three-year follow-up, no deaths occurred and there was 100% graft survival. No significant increase of adverse events was associated with ATDC infusion. Episodes of rejection were observed in two patients from the ATDC group and one patient from the control group. However, all rejections were successfully treated by glucocorticoids. Mycophenolate was successfully reduced/stopped in five patients from the ATDC group, allowing tacrolimus monotherapy for two of them. Regarding immune monitoring, reduced CD8 T cell activation markers and increased Foxp3 expression were observed in the ATDC group. Thus, our results demonstrate ATDC administration safety in kidney-transplant recipients.

Trial registration: ClinicalTrials.gov NCT02252055 NCT01656135.

Keywords: cell therapy; clinical trial; dendritic cells; tolerance; transplantation.

PubMed Disclaimer

Publication types