Oncotarget

Research Papers:

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 Andersson and Simrit Parmar _

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Oncotarget. 2018; 9:35611-35622. https://doi.org/10.18632/oncotarget.26242

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Abstract

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

Correspondence to:

Simrit Parmar, email: sparmar@mdanderson.org

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

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.


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