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Umbilical cord blood graft engineering: challenges and opportunities

Abstract

We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specificT-cells or chimeric-antigen receptor T-cells which are reviewed in this study.

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Correspondence to E J Shpall.

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LC has served as a consultant for Targazyme (formerly American Stem cells), GE Healthcare, Ferring Pharmaceuticals, Fate Therapeutics, Janssen Pharmaceuticals, and Bristol-Myers Squibb. LC owns equity/stock in Targazyme, has received lecture fees from Miltenyi Biotec and served on the Scientific Advisory Board of Cellectis. CMH has received grant support from Celgene. NDS has served on a Celgene Advisory Board and received grant support from Celgene.

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This article was published as part of a supplement, supported by WIS-CSP Foundation, in collaboration with Gilead, Milteny Biotec, Gamida cell, Adienne Pharma and Biotech, Medac hematology, Kiadis Pharma and Almog Diagnostic.

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Thompson, P., Rezvani, K., Hosing, C. et al. Umbilical cord blood graft engineering: challenges and opportunities. Bone Marrow Transplant 50 (Suppl 2), S55–S62 (2015). https://doi.org/10.1038/bmt.2015.97

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