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
| Autor: | Simrit Parmar, Jaap Jan Boelens, Joseph D. Khoury, Yago Nieto, Stefan O. Ciurea, Uday R. Popat, Richard E. Champlin, Eric Yvon, Eveline M. Delemarre, Peter F. Thall, Hongbing Ma, Sairah Ahmed, Stefan Nierkens, Jennifer D Ramos, Joshua Kellner, Borje S. Andersson, Amanda Olson, Robert S. Negrin, Zeng Ke, Mitsutaka Nishimoto, Ian K. McNiece |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Hematopoietic stem cell transplantation stem cell transplantation Umbilical cord Gastroenterology regulatory T cells Cell therapy 03 medical and health sciences Immune system Internal medicine graft versus host disease medicine Stage (cooking) business.industry medicine.disease 3. Good health Clinical trial 030104 developmental biology medicine.anatomical_structure Graft-versus-host disease Oncology umbilical cord blood cell therapy business Elafin Research Paper |
| Zdroj: | Scopus-Elsevier Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.26242 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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