🎗10-year outcomes for autologous polyclonal ex-vivo-expanded Treg cellular therapy in renal transplantation (ONE study UK Treg Trial)

Introduction: The ONE study was a multi-arm phase 1/2A trial evaluating regulatory immune cell therapies as alternatives to conventional immunosuppression in kidney transplantation. Early 60-week outcomes, published in The Lancet (2020), demonstrated feasibility and safety of regulatory T cell (Treg) therapy. 7-year follow-up showed stable graft function with the presence of atypical graft immune infiltrates distinct to those normally seen in T cell-mediated rejection. Long term Treg therapy outcomes are lacking; here we report 10-year outcomes from the UK (Oxford) arm of the ONE study.  
Method: Twenty adult living kidney transplant recipients from the Oxford arm of the ONE study were included (10 in reference group, 10 in intervention group). The reference group received basiliximab induction, tapered corticosteroids, mycophenolate mofetil (MMF), and tacrolimus. The intervention group received ex-vivo-expanded autologous Tregs, without induction immunosuppression and identical maintenance immunosuppression. Optional MMF cessation was performed in the intervention group by clinician discretion. Patients were identified through the original Oxford trial cohort. A retrospective electronic record review assessed 10-year patient and graft survival, annual creatinine and tacrolimus trough levels, biopsy-proven rejection and immunosuppression.  
Results: Baseline characteristics were similar between the two groups with comparable patient and graft survival (Table 1). Graft function diverges over time with initial creatinine values similar but improved function in the intervention group sustained over time. None of the intervention group experienced biopsy proven rejection compared to two in the reference group. Tacrolimus levels were broadly similar throughout the period. Of ten intervention patients, three remain on tacrolimus monotherapy, with no rejection episodes.

Conclusion: At 10 years, Treg therapy demonstrates comparable patient survival and graft survival relative to standard treatment. No biopsies were positive for rejection in the intervention group; immune cell infiltrates were seen but are distinct from those seen in T-cell-mediated rejection and occurred in the setting of stable graft function. These findings support long-term feasibility of regulatory cell therapy and emphasises the importance of the ongoing TWO Study to determine whether both induction and maintenance immunosuppression can be safely minimised, with the aim of reducing long-term complications such as malignancy and calcineurin inhibitor related nephrotoxicity.