Ex vivo fucosylation of third-party human regulatory T cells enhances anti-graft-versus-host disease potency in vivo

Simrit Parmar, Xiaoying Liu, Amer Najjar, Nina Shah, Hong Yang, Eric Yvon, Katy Rezvani, Ian McNiece, Patrick Zweidler-McKay, Leonard Miller, Steve Wolpe, Bruce R. Blazar, Elizabeth J. Shpall

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Adoptive therapy with regulatory T cells (Tregs) to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation. We hypothesized that adding fucose to human Tregs, forming the Sialyl Lewis X moiety on P-selectin glycoprotein ligand-1, would improve their trafficking pattern. The selectin pathway recruiter, α-1,3-fucosyltransferase-VI enzyme, significantly increased Treg surface fucosylation (66% vs 8%). In a xenogenic GVHD mouse model, fucosylated Tregs showed prolonged periods of in vivo persistence. When given at a lower dose compared with the untreated Tregs, the murine recipients of fucosylated Tregs maintained weight, had ameliorated clinical GVHD, and improved survival (70% vs 30%; P < .0001). These preclinical data indicate that fucosylated human Tregs is an effective strategy for prevention of GVHD and, as such, warrants consideration for future clinical trials.

Original languageEnglish (US)
Pages (from-to)1502-1506
Number of pages5
JournalBlood
Volume125
Issue number9
DOIs
StatePublished - 2015

Bibliographical note

Funding Information:
This work has been supported by the Anderson Cancer Center Start Up Funds and Lee Clark Award grants R01 HL11879, P01 CA065493, CA142106, and AI056299.

Publisher Copyright:
© 2015 by The American Society of Hematology.

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