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Blood. 2016 Feb 25;127(8):1044-51. doi: 10.1182/blood-2015-06-653667. Epub 2015 Nov 12.

Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect.

Author information

1
University of Minnesota Blood and Marrow Transplant Program, Division of Hematology, Oncology and Transplantation.
2
Department of Laboratory Medicine and Pathology, Molecular and Cellular Therapeutics Facility.
3
University of Minnesota Blood and Marrow Transplant Program, Division of Pediatric Blood and Marrow Transplantation, and.
4
University of Minnesota Blood and Marrow Transplant Program, Masonic Cancer Center, University of Minnesota, Minneapolis, MN;
5
University of Minnesota Blood and Marrow Transplant Program, Molecular and Cellular Therapeutics Facility.
6
Department of Pathology and Laboratory Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; and.
7
Masonic Cancer Center, University of Minnesota, Minneapolis, MN; Division of Biostatistics, University of Minnesota, Minneapolis, MN.

Abstract

We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB)-derived regulatory T cells (Tregs) that expanded in cultures stimulated with K562 cells modified to express the high-affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3-100 × 10(6) Treg/kg. The median proportion of CD4(+)FoxP3(+)CD127(-) in the infused product was 87% (range, 78%-95%), and we observed no dose-limiting infusional adverse events. Clinical outcomes were compared with contemporary controls (n = 22) who received the same conditioning regimen with sirolimus and mycophenolate mofetil immune suppression. The incidence of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 9% (95% confidence interval [CI], 0-25) vs 45% (95% CI, 24-67) in controls (P = .05). Chronic GVHD at 1 year was zero in Tregs and 14% in controls. Hematopoietic recovery and chimerism, cumulative density of infections, nonrelapse mortality, relapse, and disease-free survival were similar in the Treg recipients and controls. KT64/86-expanded UCB Tregs were safe and resulted in low risk of acute GVHD.

PMID:
26563133
PMCID:
PMC4768428
[Available on 2017-02-25]
DOI:
10.1182/blood-2015-06-653667
[Indexed for MEDLINE]
Free PMC Article

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