PMID- 30479692 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200827 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 9 IP - 86 DP - 2018 Nov 2 TI - 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. PG - 35611-35622 LID - 10.18632/oncotarget.26242 [doi] AB - 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 = 1x106/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= 1x107/kg is currently underway. FAU - Kellner, Joshua N AU - Kellner JN AD - Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Delemarre, Eveline M AU - Delemarre EM AD - Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan, CX Utrecht, The Netherlands. FAU - Yvon, Eric AU - Yvon E AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Nierkens, Stefan AU - Nierkens S AD - Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan, CX Utrecht, The Netherlands. FAU - Boelens, Jaap J AU - Boelens JJ AD - Department of Pediatrics, Stem Cell Transplant and Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - McNiece, Ian AU - McNiece I AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Olson, Amanda AU - Olson A AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Nieto, Yago AU - Nieto Y AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ciurea, Stefan AU - Ciurea S AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Popat, Uday AU - Popat U AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ahmed, Sairah AU - Ahmed S AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Champlin, Richard AU - Champlin R AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ramos, Jennifer AU - Ramos J AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Nishimoto, Mitsutaka AU - Nishimoto M AD - Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ma, Hongbing AU - Ma H AD - Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ke, Zeng AU - Ke Z AD - Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Thall, Peter AU - Thall P AD - Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Khoury, Joseph D AU - Khoury JD AD - Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Negrin, Robert AU - Negrin R AD - Division of Blood and Marrow Transplantation, Stanford University, Palo Alto, CA, USA. FAU - Andersson, Borje AU - Andersson B AD - Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Parmar, Simrit AU - Parmar S AD - Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. AD - Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - R44 CA192601/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20181102 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC6235025 OTO - NOTNLM OT - cell therapy OT - graft versus host disease OT - regulatory T cells OT - stem cell transplantation OT - umbilical cord blood COIS- CONFLICTS OF INTEREST SP is a scientific founder and serves on the board of director and chief medical officer of Cellenkos, MDACC owned startup and has a license agreement with Cellenkos. RN is a consultant for Cellenkos Inc. The remaining authors declare no conflicts of interest. EDAT- 2018/11/28 06:00 MHDA- 2018/11/28 06:01 PMCR- 2018/11/02 CRDT- 2018/11/28 06:00 PHST- 2018/08/19 00:00 [received] PHST- 2018/10/06 00:00 [accepted] PHST- 2018/11/28 06:00 [entrez] PHST- 2018/11/28 06:00 [pubmed] PHST- 2018/11/28 06:01 [medline] PHST- 2018/11/02 00:00 [pmc-release] AID - 26242 [pii] AID - 10.18632/oncotarget.26242 [doi] PST - epublish SO - Oncotarget. 2018 Nov 2;9(86):35611-35622. doi: 10.18632/oncotarget.26242. eCollection 2018 Nov 2.