Evidence map›Paper›PMID 36804930›Full record

ArticleTransplantation and cellular therapy2023

Regulatory T Cell Amelioration of Graft-versus-Host Disease following Allogeneic/Xenogeneic Hematopoietic Stem Cell Transplantation Using Mobilized Mouse and Human Peripheral Blood Donors.

Henry Barreras, Sabrina N Copsel, Cameron S Bader, Ying Ding, Dietlinde Wolf, Charles Cash, Caleb J Stacey, Cara Benjamin, Mathew M Seavey, Jeffrey Wolf and 7 more

Abstract read
In one paragraph

Article in Transplantation and cellular therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Henry BarrerasDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida.
Sabrina N CopselDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida.
Cameron S BaderDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida.
Ying DingDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida.
Dietlinde WolfSylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida.
Charles CashDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida.
Caleb J StaceyDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida.
Cara BenjaminSylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida.
Mathew M SeaveyNightHawk Biosciences Inc/Pelican Therapeutics, Inc, Morrisville, North Carolina.
Jeffrey WolfNightHawk Biosciences Inc/Pelican Therapeutics, Inc, Morrisville, North Carolina.
Rahul R JasujaNightHawk Biosciences Inc/Pelican Therapeutics, Inc, Morrisville, North Carolina.
Brent PfeifferDepartment of Pediatrics, University of Miami School of Medicine, Miami, Florida.
Geoffrey R HillFred Hutchinson Cancer Research Center, Seattle, Washington.
Krishna V KomanduriDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida; Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida; Division of Transplantation and Cellular Therapy, Department of Medicine, University of Miami School of Medicine, Miami, Florida.
Roland JurecicDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida; Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida.
Thomas R MalekDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida.
Robert B LevyDepartment of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida; Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida; Department of Ophthalmology, University of Miami School of Medicine, Miami, Florida. Electronic address: rlevy@med.miami.edu.

Funding

Immune Mechanisms in Ocular Graft versus Host DiseaseR01EY024484 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LEVY, ROBERT BENJAMIN, PEREZ, VICTOR L · 2014 to 2025
$5.1M
Local regulation and deletion of T cells to induce tolerance and establish long-term survival of high-risk corneal transplantsR01EY030283 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Robert Benjamin Levy, Victor L Perez · 2020 to 2026
$3.1M
(PQ9) Characterization and prophylactic treatment of chemotherapy-induced long-term adverse sequelaeR01CA208634 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI JURECIC, ROLAND · 2016 to 2020
$2.8M
The regulation of innate immune sensors to control GVHD and GVL after allogeneic hematopoietic stem cell transplantationK00CA245728 · NCI · STANFORD UNIVERSITY · PI BADER, CAMERON SCOTT · 2021 to 2024
$372k
Application of TNFRSF25 agonists for prophylaxis and treatment of graft versus host diseaseR41AI149916 · NIAID · PELICAN THERAPEUTICS, INC. · PI SEAVEY, MATTHEW · 2020 to 2020
$225k
NCI NIH HHS K00 CA245728NCI NIH HHS R01 CA208634NEI NIH HHS R01 EY024484NEI NIH HHS R01 EY030283NIAID NIH HHS R41 AI149916
6 · The paper itself

Abstract

The present studies examined experimental transplant outcomes using mobilized peripheral blood from mice and humans together with FoxP3+Treg cells. Donor mice were treated with filgrastim and / or plerixafor and their peripheral blood (PB) displayed significant elevations in hematopoietic stem and progenitor populations. Some of these PB donors were concurrently administered a Treg expansion strategy consisting of a TL1A-Ig fusion protein low dose rIL-2. A significant increase (4-5x) in the frequency Tregs occurred during mobilization. C3H.SW PB was collected from mobilized and Treg unexpanded ("TrUM") or mobilized and Treg expanded ("TrEM") donors and transplanted into MHC-matched B6 (H2b) recipients. Recipients of TrEM, exhibited significantly reduced weight loss and clinical GVHD scores compared to recipients of TrUM. Notably, recipients of TrEM exhibited comparable GVL activity to TrUM recipients against leukemia levels. Next, huTregs (CD4+CD25+CD127lo) from a healthy human PB mobilized donor were expanded ex-vivo prior to transplant into NSG/ NOD-scid IL2Rgammanull mice. We found that treatment with ex-vivo expanded huTregs resulted in significant reduction of lethality and clinical xGVHD scores. Notably, post-transplant, PB huTregs levels remained elevated and the frequency of huCD4+Tconv and CD8+ cells was diminished supporting the improved xGVHD outcomes. These findings demonstrated that the use of mPB containing elevated Treg levels significantly reduced GVHD following "MUD" and MHC-mismatched mouse HSCT without loss of GVL activity. Moreover, utilizing ex-vivo expanded huTregs from a mobilized PB donor and added back to donor PB ameliorated xGVHD. In total, these studies support the notion that in vivo or ex-vivo manipulation of donor Tregs together with mobilized peripheral blood could provide therapeutic approaches to improve aHSCT outcomes.

Indexed as

Graft vs Host DiseaseHematopoietic Stem Cell TransplantationHeterocyclic CompoundsAnimalsBlood DonorsHematopoietic Stem Cell MobilizationHumansMiceMice, Inbred C3HMice, Inbred NODProteinsT-Lymphocytes, RegulatoryHeterocyclic CompoundsProteinsAllogeneic Hematopoietic Stem Cell TransplantationGraft-versus-Host DiseaseGVT, XenotransplantationMobilizationTL1ATregs, IL-2

Identifiers

PMID36804930
PMCPMC10149591

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.