Sequential Targeting of CD52 and TNF Allows Early Minimization Therapy in Kidney Transplantation: From a Biomarker to Targeting in a Proof-Of-Concept Trial

Abstract : BACKGROUND: There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy. METHODS: In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months. RESULTS: TAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6-98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up. CONCLUSIONS: In conclusion, our novel fast-track TAC-monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full-scale study will be needed to confirm our findings.
Document type :
Journal articles
Complete list of metadatas

Cited literature [47 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02153723
Contributor : Ana Paula Dutra Azevedo <>
Submitted on : Wednesday, June 12, 2019 - 2:16:43 PM
Last modification on : Thursday, July 11, 2019 - 2:10:09 PM

File

pone.0169624.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Ondrej Viklicky, Petra Hruba, Stefan Tomiuk, Sabrina Schmitz, Bernhard Gerstmayer, et al.. Sequential Targeting of CD52 and TNF Allows Early Minimization Therapy in Kidney Transplantation: From a Biomarker to Targeting in a Proof-Of-Concept Trial. PLoS ONE, Public Library of Science, 2017, 12 (1), pp.e0169624. ⟨10.1371/journal.pone.0169624⟩. ⟨inserm-02153723⟩

Share

Metrics

Record views

157

Files downloads

40