Date: Sunday, June 2, 2019
Session Time: 2:30pm-4:00pm
Presentation Time: 3:30pm-3:42pm
Location: Room 306
*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+CD25highCD127low 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.
To cite this abstract in AMA style:Sawitzki B, Schlickeiser S, Streitz M, Jürchott K, Hutchinson J, Geissler E, Investigators P. One Study: A Consortium Model of Clinical Trials Optimized for Comparing New Immune Therapies via Centralized Immune Monitoring [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/one-study-a-consortium-model-of-clinical-trials-optimized-for-comparing-new-immune-therapies-via-centralized-immune-monitoring/. Accessed November 23, 2020.
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