Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution
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Joshua N. Kellner1, Eveline M. Delemarre2, Eric Yvon3, Stefan Nierkens2, Jaap J. Boelens4, Ian McNiece3, Amanda Olson3, Yago Nieto3, Stefan Ciurea3, Uday Popat3, Sairah Ahmed3, Richard Champlin3, Jennifer Ramos3, Mitsutaka Nishimoto5, Hongbing Ma5, Zeng Ke5, Peter Thall6, Joseph D. Khoury7, Robert Negrin8, Borje Andersson3 and Simrit Parmar1,5
1Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
2Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan, CX Utrecht, The Netherlands
3Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA
4Department of Pediatrics, Stem Cell Transplant and Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York, NY, USA
5Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA
6Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
7Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
8Division of Blood and Marrow Transplantation, Stanford University, Palo Alto, CA, USA
Simrit Parmar, email: [email protected]
Keywords: regulatory T cells; umbilical cord blood; graft versus host disease; cell therapy; stem cell transplantation
Received: August 19, 2018 Accepted: October 06, 2018 Published: November 02, 2018
Incubation of umbilical cord blood (UCB) derived regulatory T-cells (Tregs) with fucosyltransferase enzyme improves their ability to home to the target tissue to prevent graft vs. host disease (GVHD). We report results of 5 patients (Double UCB Transplant, n=2; Peripheral Blood Matched Unrelated Donor Transplant, n=3) who received UCB-Tregs (Dose level = 1×106/kg), infused one day prior to the donor graft. All patients received their designated UCB-Treg dose without any infusion reaction. The ratio of conventional T-cells in donor graft was at least 10 times higher than infused UCB-Tregs (ratio range, 12-356). All patients engrafted at median of 13 days (range, 8-17 days). One patient died due to brain hemorrhage on day 45. A bi-modal increase of plasma IL-10 level occurred on day 7 and day 21 and notably, plasma IL-2 level dropped significantly in all patients at Day 7. All evaluable patients developed ≥grade II acute GVHD and at 1 year follow up, all were alive and without evidence of disease relapse. No increase in the chronic GVHD biomarkers (REG3a and Elafin) was observed at day 7. At the time of last follow up, all evaluable patients were off immune-suppression. Stage 2 of this clinical trial examining UCB-Treg at dose level= 1×107/kg is currently underway.
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