Abstract: FR-OR137
A Phase-I Clinical Trial of Donor-Derived MIC Cell Infusion for the Induction of Donor-Specific Hyporesponsiveness after Living Donor Kidney Transplantation (TOL-1 Study)
Session Information
- Translational and Transplant Pathology
October 26, 2018 | Location: 6E, San Diego Convention Center
Abstract Time: 05:30 PM - 05:42 PM
Category: Transplantation
- 1802 Transplantation: Clinical
Authors
- Morath, Christian, Heidelberg University Hospital, Heidelberg, Germany
- Schmitt, Anita, Heidelberg University Hospital, Heidelberg, Germany
- Kleist, Christian, Heidelberg University Hospital, Heidelberg, Germany
- Daniel, Volker, Heidelberg University Hospital, Heidelberg, Germany
- Opelz, Gerhard, Heidelberg University Hospital, Heidelberg, Germany
- Süsal, Caner, Heidelberg University Hospital, Heidelberg, Germany
- Kälble, Florian, Heidelberg University Hospital, Heidelberg, Germany
- Speer, Claudius, Heidelberg University Hospital, Heidelberg, Germany
- Pego silva, Luiza, Heidelberg University Hospital, Heidelberg, Germany
- Sommerer, Claudia, Heidelberg University Hospital, Heidelberg, Germany
- Wang, Lei, Heidelberg University Hospital, Heidelberg, Germany
- Hückelhoven-Krauss, Angela, Heidelberg University Hospital, Heidelberg, Germany
- Merle, Uta, Heidelberg University Hospital, Heidelberg, Germany
- Mehrabi, Arianeb, Heidelberg University Hospital, Heidelberg, Germany
- Mueller-Tidow, Carsten, Heidelberg University Hospital, Heidelberg, Germany
- Zeier, Martin G., Heidelberg University Hospital, Heidelberg, Germany
- Schmitt, Michael, Heidelberg University Hospital, Heidelberg, Germany
- Schaier, Matthias, Heidelberg University Hospital, Heidelberg, Germany
- Terness, Peter, Heidelberg University Hospital, Heidelberg, Germany
Background
MIC cells are donor-derived monocytes that gain immunosuppressive properties after incubation with the proliferation inhibitor mitomycin C.
Methods
PBMCs were harvested from living donors by leukapheresis and MIC cells were manufactured under GMP conditions.Transplant recipients received either 1.5x10E6 MIC cells/kg body weight on day -2 (N=3,group A), 1.5x10E8 MIC cells/kg body weight on day -2 (N=3,group B) or day -7 (N=4,group C) before living donor kidney transplantation.Patients received immunosuppressive therapy with CyA,EC-MPS and CS.Primary outcome measure was the frequency of adverse events (AE) on day 30.
Results
A total of 72 AEs (3 severe AEs) occurred in treated patients that were unrelated to MIC cell infusion.No positive cross match results, de novo donor specific antibodies, or rejection episodes but 2 infectious complications were recorded.Median serum creatinine on day 30 was 1.4 mg/dL with no significant proteinuria.In vitro,MIC cells were capable of inducing tolerogenic dendritic cells with low expression of costimulatory molecules CD80, CD86 and a 30% increase of immunosuppressive molecule CD103.Beyond day 30 after surgery, serum creatinine remained stable (median 1.48 mg/dL on day 180) with no significant proteinuria (median 10 g/mol creatinine on day 180) and no rejection episodes.The patients from group C who received low-dose CyA and low-dose EC-MPS during the observation phase had no or only minimal reactivity against irradiated donor lymphocytes in mixed lymphocyte culture while reactivity against 3rd party lymphocytes was preserved.CD19+ B cells increased to a median of 300/µL until day 30 but decreased to a median of 35/µL on day 180.CD19+CD24highCD38high transitional Bregs increased from a median of 2% on day 30 to a median of 20% of the total CD19+ B cell pool on day 180.There was an increase in the plasma IL-10/TNFalpha ratio from a median of 0.05 before cell therapy to a median of 0.11 on day 180.
Conclusion
MIC cell therapy represents a promising option for individualized immunosuppression after living donor kidney transplantation.