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

نویسندگان

  • Ondrej Viklicky
  • Petra Hruba
  • Stefan Tomiuk
  • Sabrina Schmitz
  • Bernhard Gerstmayer
  • Birgit Sawitzki
  • Patrick Miqueu
  • Petra Mrazova
  • Irena Tycova
  • Eva Svobodova
  • Eva Honsova
  • Uwe Janssen
  • Hans-Dieter Volk
  • Petra Reinke
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Cancer virotherapy: Targeting cancer cells by microRNA mechanism for selective replication of oncolytic viruses in these cells

Cancer, as one of the most serious public health problems, is the second-leading cause of death in the world after cardiovascular disease. The number of patients and the resulting mortality are increasing worldwide; therefore, early diagnosis, prevention, and effective treatment of cancer are very important. Current treatments such as chemotherapy and radiation therapy are often non-selective a...

متن کامل

The Effect of Acceptance and Commitment Based Group Therapy on Increasing the Quality of Life in Kidney Transplant and Hemodialysis Patients in Zanjan City: A Randomized Clinical Trial Study

Background and Objectives: kidney diseases threaten mental and physical health. Acceptance and commitment therapy is a third generation treatment that affects life quality of patients. The present research aimed at determining the effect of acceptance and commitment based therapy on life quality of homodialized and kidney transplant patients in Zanjan city. Materials and Methods: This was a ra...

متن کامل

P-216: Dual Targeting of TNF-? and Free Radicals Toxic Stress as A Promising Strategy to Manage Experimental Polycystic Ovary

متن کامل

Effect of Hypertonic Saline 5% on Early Graft Function and Urinary Interleukin 18 and Neutrophil Gelatinase-Associated Lipocalin in Deceased-Donor Kidney Transplantation

Ischemia reperfusion injury (IRI) is one of the main causes of delay graft function (DGF) in deceased-donor kidney transplantation (DDKT). Evidences suggest that hypertonic saline (HS) has beneficial effects on IRI. The objective of the present study is to determine the effect of intraoperative HS, on graft function and urinary biomarkers of interleukin 18 (IL-18) and neutrophil gelatinase-asso...

متن کامل

Combination therapy with everolimus and tacrolimus in kidney transplantation recipients: A systematic review

Background and aims: Immunosuppressive regimens are a key component for successful kidney transplantation. This systematic review aimed to assess the efficacy and safety of combination therapy of everolimus with tacrolimus in kidney transplantation recipients. Methods: Results were limited to English-language articles. Trials where recipients received ano...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 12  شماره 

صفحات  -

تاریخ انتشار 2017