*Purpose: Immune regulatory cell subpopulations can potentially control immune responses to allow immunosuppression (IS) drug minimization. In the ONE Study, an EU FP7-funded research group is testing different regulatory cell products under a common IS protocol. The ONE Study offers a model for optimizing immune monitoring (IM) for novel immunotherapy trials.

*Methods: Living-donor renal transplant (Tx) patients were treated: (1) with conventional IS only (“CI”; n=67: basiliximab induction, with tacrolimus / MMF + steroids weaned by mo. 3) in one multicenter trial (8 sites in Europe + USA) , or (2) with the same IS (minus basiliximab induction) + one of 6 different regulatory cell products (Treg, tolDC, or Mreg: “CTP”s, n=38) in 6 separate trials among the same sites. Centrally controlled IM was performed at designated pre and post-Tx visits: results from local whole blood flow cytometry and central gene expression analysis are given here.

*Results: Comparative analysis of healthy control (n=92) and pre-Tx CI samples revealed relative and absolute increases in inflammatory CD16⁺ monocyte and myeloid DC populations, with decreases in pDCs and marginal zone-like B cells (consistent with inflammation in ESRD patients); conventional therapy in CI patients did not lead to normalization after Tx. Interestingly, CI patients experiencing rejection had higher pre-Tx numbers of CD4⁺CD25^highCD127^low Treg and increased transcription of CD200, FCRL2 and NAV3. Remarkably, pre-Tx Tregs and post-Tx (mo. 2) CD16⁺ monocytes and DCs correlated negatively with graft function (eGFR) at study end (mo. 15). Pre-Tx comparison of local, site-specific CI and CTP patients revealed a bias in IM data. To remove bias, we developed a bioinformatics tool to match patients from the CI multicenter study with highly similar CTP patients, allowing meaningful comparison of post-Tx changes between CI and CTP patients. This revealed normalization of immune parameters in CTP patients.

*Conclusions: In a consortium setting with centralized IM data on a large number of control patients in a multicenter trial, interesting immune response patterns emerge, allowing new immunotherapies in separate small trials to be evaluated and compared if they use similar patient cohorts and background IS.

« Back to 2019 American Transplant Congress