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Article Dans Une Revue Kidney International Année : 2022

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

1 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
2 Team 1 - U1064 Inserm - CR2TI - Team 1 : Mononuclear phagocytes, Immunopathology, Immunovirology
3 Nantes Univ - Nantes Université
4 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
5 Team 3 - U1064 Inserm - CR2TI - Team 3 : Integrative transplantation, HLA, Immunology and genomics of kidney injury
6 ITUN - Institut de transplantation urologie-néphrologie
7 Service de Néphrologie et Immunologie Clinique [CHU de Nantes]
8 UTCG - Unité de Thérapie Cellulaire et Génique [CHU Nantes]
9 CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
10 UMR 1064 Centre de Recherche en Transplantation et Immunologie
11 UMR 1064, ITUN - Institut de Transplantation Urologie Nephrologie
12 Nantes Univ - ECN - NANTES UNIVERSITÉ - École Centrale de Nantes
13 CRCI2NA / Eq 2 - Nuclear Oncology
14 CIC Nantes - Centre d’Investigation Clinique de Nantes
15 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
16 FLI - Friedrich-Loeffler-Institut
17 University of Regensburg
18 Oxford University Hospitals NHS Trust
19 Guy's and St Thomas' Hospital [London]
20 UC San Francisco - University of California [San Francisco]
21 Massachusetts General Hospital [Boston]
22 University Hospital Regensburg
23 Fraunhofer ITEM - Fraunhofer Institute for Toxicology and Experimental Medicine
24 INCIT - Immunology and New Concepts in ImmunoTherapy
25 Service de dermatologie [Nantes]
26 LabEX IGO Immunothérapie Grand Ouest

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.

Dates et versions

inserm-03965853 , version 1 (31-01-2023)

Identifiants

Citer

Aurélie Moreau, Delphine Kervella, Laurence Bouchet-Delbos, Cécile Braudeau, Soraya Saïagh, et al.. A Phase I/IIa study of autologous tolerogenic dendritic cells immunotherapy in kidney transplant recipients. Kidney International, 2022, pp.S0085-2538(22)00845-6. ⟨10.1016/j.kint.2022.08.037⟩. ⟨inserm-03965853⟩
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