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

Humans Tacrolimus / therapeutic use Mycophenolic Acid / therapeutic use Kidney Transplantation / adverse effects Transplant Recipients Immunosuppressive Agents / therapeutic use Immunosuppression Therapy / methods Dendritic Cells Graft Rejection Graft Survival

cell therapy clinical trial dendritic cells tolerance transplantation

Journal

Kidney international

ISSN: 1523-1755

Titre abrégé: Kidney Int

Pays: United States

ID NLM: 0323470

Informations de publication

Date de publication:
03 2023

Historique:

received: 22 03 2022

revised: 16 08 2022

accepted: 19 08 2022

pubmed: 29 10 2022

medline: 3 3 2023

entrez: 28 10 2022

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.kint.2022.08.037 PMID: 36306921

pubmed: 36306921

pii: S0085-2538(22)00845-6

doi: 10.1016/j.kint.2022.08.037

pii:

doi:

Substances chimiques

Tacrolimus WM0HAQ4WNM

Mycophenolic Acid HU9DX48N0T

Immunosuppressive Agents 0

Banques de données

ClinicalTrials.gov

['NCT02252055', 'NCT01656135']

EudraCT

['2014-000208-82', '2011-004301-24']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

627-637

Investigateurs

Gilles Blancho (G)

Julien Branchereau (J)

Diego Cantarovich (D)

Agnès Chapelet (A)

Jacques Dantal (J)

Clément Deltombe (C)

Lucile Figueres (L)

Raphael Gaisne (R)

Claire Garandeau (C)

Magali Giral (M)

Caroline Gourraud-Vercel (C)

Maryvonne Hourmant (M)

Georges Karam (G)

Clarisse Kerleau (C)

Delphine Kervella (D)

Christophe Masset (C)

Aurélie Meurette (A)

Simon Ville (S)

Christine Kandell (C)

Anne Moreau (A)

Karine Renaudin (K)

Florent Delbos (F)

Alexandre Walencik (A)

Anne Devis (A)