Evidence map›Paper›PMID 31810768›Full record

ArticleCytotherapy2019

Cryopreservation timing is a critical process parameter in a thymic regulatory T-cell therapy manufacturing protocol.

Katherine N MacDonald, Sabine Ivison, Keli L Hippen, Romy E Hoeppli, Michael Hall, Grace Zheng, I Esme Dijke, Mohammed Al Aklabi, Darren H Freed, Ivan Rebeyka and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cytotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
–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

20 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  11. Molecular therapy. Methods & clinical development · 2023
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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

15 authors.

Katherine N MacDonaldSchool of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada; BC Children's Hospital Research Institute, Vancouver, BC, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Sabine IvisonBC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
Keli L HippenDepartment of Pediatrics, Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis/Saint Paul, Minnesota, USA.
Romy E HoeppliBC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
Michael HallBC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
Grace ZhengBC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
I Esme DijkeDepartment of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada; Alberta Transplant Institute, University of Alberta, Edmonton, AB, Canada.
Mohammed Al AklabiDepartment of Surgery, University of Alberta, Edmonton, AB, Canada.
Darren H FreedAlberta Transplant Institute, University of Alberta, Edmonton, AB, Canada; Department of Surgery, University of Alberta, Edmonton, AB, Canada.
Ivan RebeykaDepartment of Surgery, University of Alberta, Edmonton, AB, Canada.
Sanjiv GandhiBC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
Lori J WestAlberta Transplant Institute, University of Alberta, Edmonton, AB, Canada; Department of Surgery, University of Alberta, Edmonton, AB, Canada; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
James M PiretSchool of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada; Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, Canada.
Bruce R BlazarDepartment of Pediatrics, Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis/Saint Paul, Minnesota, USA.
Megan K LevingsSchool of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada; BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada. Electronic address: mlevings@bcchr.ca.

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Project 3: Humoral Targets and B Cell Biology in Chronic Graft-vs.-Host DiseaseP01CA142106 · NCI · DANA-FARBER CANCER INST · PI CUTLER, COREY S · 2009 to 2019
$17.5M
Enhancing Treg Therapeutic Efficacy in GVHDR01HL118979 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, HIPPEN, KELI L · 2014 to 2025
$6.7M
T-CELL TARGETING FOR GVHDR01HL056067 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1995 to 2022
$5.4M
In Vivo Prevention of Murine GVHDR37AI034495 · NIAID · UNIVERSITY OF MINNESOTA · PI Bruce R Blazar · 2017 to 2026
$5.4M
CIHR TFU 127880NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA142106NHLBI NIH HHS R01 HL056067NHLBI NIH HHS R01 HL118979NIAID NIH HHS R37 AI034495
6 · The paper itself

Abstract

Regulatory T cells (Tregs) are a promising therapy for several immune-mediated conditions but manufacturing a homogeneous and consistent product, especially one that includes cryopreservation, has been challenging. Discarded pediatric thymuses are an excellent source of therapeutic Tregs with advantages including cell quantity, homogeneity and stability. Here we report systematic testing of activation reagents, cell culture media, restimulation timing and cryopreservation to develop a Good Manufacturing Practice (GMP)-compatible method to expand and cryopreserve Tregs. By comparing activation reagents, including soluble antibody tetramers, antibody-conjugated beads and artificial antigen-presenting cells (aAPCs) and different media, we found that the combination of Dynabeads Treg Xpander and ImmunoCult-XF medium preserved FOXP3 expression and suppressive function and resulted in expansion that was comparable with a single stimulation with aAPCs. Cryopreservation tests revealed a critical timing effect: only cells cryopreserved 1-3 days, but not >3 days, after restimulation maintained high viability and FOXP3 expression upon thawing. Restimulation timing was a less critical process parameter than the time between restimulation and cryopreservation. This systematic testing of key variables provides increased certainty regarding methods for in vitro expansion and cryopreservation of Tregs. The ability to cryopreserve expanded Tregs will have broad-ranging applications including enabling centralized manufacturing and long-term storage of cell products.

Indexed as

Cell- and Tissue-Based TherapyCell Culture TechniquesCell ProliferationCells, CulturedChild, PreschoolCryopreservationCulture MediaHumansInfantLymphocyte ActivationManufactured MaterialsThymus GlandTime FactorsTissue EngineeringT-Lymphocytes, RegulatoryCulture Mediacell therapycryopreservationGood Manufacturing Practiceregulatory T cellT-cell manufacturingtolerance

Identifiers

PMID31810768
PMCPMC7474528

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Registered trials

None linked

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.