Donor-derived regulatory dendritic cell infusion and early immunosuppressive drug withdrawal in living-donor liver transplantation: a phase I/IIa trial

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: 37.5% operational tolerance rate in withdrawal-eligible recipients vs 13% historical rate

• Primary Outcome: ddDCreg infusions were safe, reproducible, and well-tolerated

• Nnt Or Sensitivity: Number needed to treat approximately 4 patients to achieve one additional case of operational tolerance compared to historical controls

• Confidence Interval: Not reported

Clinical Application

Requires sophisticated cell processing facilities and expertise; limited to specialised transplant centres Would require TGA approval for cell therapy; limited to major transplant centres with cell processing capabilities; potential PBS consideration for cost-effectiveness Highly selected living-donor liver transplant recipients with quiescent protocol biopsies at 1 year

Abstract

Operational tolerance (OT) following complete immunosuppression withdrawal (ISW) is rare ( ~ 13%) in eligible adult liver transplant recipients when initiated 1-2-years post-transplant. Regulatory dendritic cells (DCregs) promote transplant tolerance in pre-clinical models and attenuate immune effector cells in humans. Here, we completed a first-in-human phase I/IIa trial (2-year recruitment; 5 ± 0.5 years follow-up) to evaluate the feasibility, safety and preliminary efficacy of pre-emptive donor-derived DCreg (ddDCreg) infusion 7-days pre-transplant in 15 prospective living-donor liver recipients. Two patients were excluded from analysis for reasons unrelated to the study. ISW began one year post-transplant in candidates with a quiescent/permissive protocol biopsy. ddDCreg infusions were safe, reproducible, and well-tolerated. One-year post-transplant, 8/13 patients were eligible for ISW, 4 achieved complete ISW, 3 remained off all immunosuppression for >1 year. These 3 remained drug-free for 3.0 ± 0.17-years, reflecting a 37.5% OT rate in ISW-eligible recipients. Given the exploratory nature of this trial, additional studies to evaluate efficacy are needed. ClinicalTrials.gov registration number NCT03164265.

References

1. 1.Humar, A., Hadjiyannis, Y., Macedo, C., Tran, L. M., Elinoff, B. D., Hughes, C. B., Ganesh, S. R., Zahorchak, A. F., Ables, E. M., Styn, M. A., Landsittel, D., Zeevi, A., Lakkis, F. G., Metes, D. M., & Thomson, A. W. (2026). Donor-derived regulatory dendritic cell infusion and early immunosuppressive drug withdrawal in living-donor liver transplantation: a phase I/IIa trial. Nature Communications. https://doi.org/10.1097/TP.0b013e31821cdf0d