title: Ex vivo fucosylation of third-party human regulatory T cells enhances anti-graft-versus-host disease potency in vivo.
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.
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapy.
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapy.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cancer Systems Imaging, and.
authors.forename: Amer
authors.initials: A
authors.lastname: Najjar
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapy.
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapy.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapy.
authors.forename: Eric
authors.initials: E
authors.lastname: Yvon
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapy.
authors.forename: Katy
authors.initials: K
authors.lastname: Rezvani
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapy.
authors.forename: Ian
authors.initials: I
authors.lastname: McNiece
authors.affiliation: Department of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston, TX;
authors.forename: Patrick
authors.initials: P
authors.lastname: Zweidler-McKay
authors.affiliation: Targazyme Inc., Carlsbad, CA; and.
authors.forename: Leonard
authors.initials: L
authors.lastname: Miller
authors.affiliation: Targazyme Inc., Carlsbad, CA; and.
authors.forename: Steve
authors.initials: S
authors.lastname: Wolpe
authors.affiliation: Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: Department of Stem Cell Transplant and Cellular Therapy.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009844:Oligosaccharides / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D019040:E-Selectin; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; C084882:P-selectin ligand protein; D000080506:Sialyl Lewis X Antigen; D005643:Fucose; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase