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

Joshua N. Kellner, Eveline M. Delemarre, Eric Yvon, Stefan Nierkens, Jaap J. Boelens, Ian McNiece, Amanda Olson, Yago Nieto, Stefan Ciurea, Uday Popat, Sairah Ahmed, Richard Champlin, Jennifer Ramos, Mitsutaka Nishimoto, Hongbing Ma, Zeng Ke, Peter Thall, Joseph D. Khoury, Robert Negrin, Borje AnderssonSimrit Parmar

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)35611-35622
Number of pages12
JournalOncotarget
Volume9
Issue number86
DOIs
Publication statusPublished - 1 Nov 2018
Externally publishedYes

Keywords

  • Cell therapy
  • Graft versus host disease
  • Regulatory T cells
  • Stem cell transplantation
  • Umbilical cord blood

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