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PLoS One. 2017 Jan 13;12(1):e0169624. doi: 10.1371/journal.pone.0169624. eCollection 2017.

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

Author information

1
Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
2
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
3
Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
4
Institute of Medical Immunology, Charité University Medicine Berlin, Germany.
5
Berlin-Brandenburg Center for Regenerative Medicine (BCRT), Charité University Medicine Berlin, Germany.
6
Institut National de la Santé et de la Recherche Médicale INSERM U1064, France.
7
Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France.
8
Department of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
9
Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
10
Department of Nephrology and Intensive Care Medicine, Charité University Medicine Berlin, Germany.

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.

TRIAL REGISTRATION:

EudraCT Number: 2006-003110-18.

PMID:
28085915
PMCID:
PMC5234822
DOI:
10.1371/journal.pone.0169624
[Indexed for MEDLINE]
Free PMC Article

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