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This is a study to assess cell therapy as a treatment to prevent kidney transplant rejection. Patients will be randomly assigned to either receive standard medication after transplant or a modified regimen including the cell product.

Patients receiving kidney transplants must take multiple medications to prevent rejection. These medicines are essential and highly effective but, in the long-term, carry with them life-threatening and life-limiting side-effects such as severe infections, cancer, heart disease and diabetes.  A major goal in transplantation is the minimisation of the need for these medications and their associated side-effects whilst still protecting the transplant from rejection. 

Our blood contains a group of white blood cells called Regulatory T cells or Tregs.  These cells exist to prevent our immune system from attacking our own body and to prevent excessive immune responses to infections that might otherwise result in harm.  These natural Treg cells have been shown in experimental models to be able to prevent transplant rejection and we are aiming to demonstrate that this might be possible in patients receiving kidney transplants.  

In our study we will take blood from patients prior to transplantation, identify and purify the Treg cells and then expand them in the laboratory to far greater numbers.  We will then give this greater number of cells back through a drip into the blood stream after kidney transplantation in a bid to tip the balance of the body away from a transplant rejection response.  We hope this new treatment will mean patients only need one medication to prevent rejection and will benefit from reduced medication side-effects in the long-term.

Summary

The TWO Study is a single centre phase IIb randomised controlled trial of regulatory T cell therapy in renal transplantation.  In this study we will obtain naturally occurring regulatory T cells (Treg) from patients prior to transplantation and expand such cells to far greater numbers in the laboratory.  The expanded cells will then be re-infused into the transplant recipient 6 months post-transplantation.  We aim to demonstrate that this approach will tip the balance of the immune system away from transplant rejection and allow us to reduce the need for pharmaceutical immunosuppression which carries with it intrinsic, life-limiting, side effects.

Background

Patients undergoing organ transplantation are required to take life-long medication to prevent rejection.  Whilst such medications are essential and highly effective they carry with them a substantial burden of side-effects including an increased risk of life-threatening events such as severe infection, heart disease, cancer and diabetes.  Numerous experimental models have demonstrated that naturally occurring regulatory T cells (Treg) may be used to prevent the rejection of transplanted organs and there is now great interest in bringing cell therapy into the clinical setting.  We have previously taken part in a phase 1 trial of regulatory T cell infusion in kidney transplantation, The ONE Study.  The ONE Study isolated naturally occurring Treg from patients due to undergo living donor kidney transplantation.  Treg were subsequently expanded to far greater numbers in the laboratory and then re-infused into the same patient after transplantation in a dose escalation manner.  The ONE Study demonstrated that Treg infusion could be performed successfully and safely.  We are now looking to expand our experience through The TWO Study.  The TWO Study aims to demonstrate that we might utilise infusions of expanded Treg to reduce the need for anti-rejection medications and therefore reduce exposure to their intrinsic life-limiting side-effects.

Aims and Objectives

To compare the efficacy of autologous regulatory T cell therapy used in conjunction with tacrolimus to standard of care immunosuppression (MMF and tacrolimus) in preventing acute biopsy-proven rejection in renal transplant recipients.

Study Design

Single-centre, open-label, randomised-controlled Phase IIb trial in 68 patients.

 

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Funded by

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