This data is for laboratory research purposes only. Not for human or animal consumption.
What is Donor-Derived Dendritic Cell Regulatory (ddDCreg) Infusion Therapy?
Donor-derived dendritic cell regulatory (ddDCreg) infusion is a pre-emptive cellular immunotherapy administered 7 days pre-transplant to promote operational tolerance in liver transplant recipients. This first-in-human trial demonstrates that ddDCreg therapy can facilitate immunosuppression withdrawal (ISW) in a subset of eligible recipients, achieving a 37.5% operational tolerance rate—significantly higher than the baseline 13% rate observed without intervention.
Mechanism of Action
Regulatory dendritic cells (DCregs) suppress immune effector cell activity through tolerogenic pathways that promote transplant acceptance. In this trial, donor-derived DCregs are hypothesized to establish a permissive immunological microenvironment that allows hepatic allograft acceptance without sustained pharmacological immunosuppression. The pre-transplant timing (7 days pre-graft placement) enables DCregs to prime tolerogenic responses before alloantigen exposure, enhancing the likelihood of achieving a quiescent graft phenotype amenable to drug withdrawal.
Observed Laboratory Results
- 37.5% operational tolerance rate (3/8 ISW-eligible recipients achieved complete immunosuppression withdrawal and remained drug-free for 3.0 ± 0.17 years), compared to ~13% baseline OT rate without ddDCreg intervention
- 100% safety and tolerability profile: ddDCreg infusions were reproducible, well-tolerated, and produced no reported adverse events attributable to cellular therapy in 15 enrolled recipients (13 analyzed)
- Expansion of ISW candidacy: 61.5% of recipients (8/13) achieved protocol-defined quiescent/permissive biopsy criteria at one year post-transplant, enabling formal immunosuppression withdrawal initiation
Clinical Significance
This phase I/IIa trial (NCT03164265) provides proof-of-concept that pre-emptive ddDCreg therapy in living-donor liver transplantation can substantially increase operational tolerance rates in carefully selected recipients. The 37.5% OT achievement in ISW-eligible patients represents a 2.9-fold improvement over historical controls, supporting the feasibility of tolerance-inducing cellular approaches in solid organ transplantation.