ArticleCytotherapy2017
Optimization of cGMP purification and expansion of umbilical cord blood-derived T-regulatory cells in support of first-in-human clinical trials.
Article in Cytotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Trial
- CRISPR/Cas9 deletion of MIR155HG in human T cells reduces incidence and severity of acute GVHD in a xenogeneic model.Blood advances · 2024Article
- Clinical Manufacturing of Regulatory T Cell Products For Adoptive Cell Therapy and Strategies to Improve Therapeutic Efficacy.Organogenesis · 2023Review
- Therapeutic Perspectives for the Clinical Application of Umbilical Cord Hematopoietic and Mesenchymal Stem Cells: Overcoming Complications Arising After Allogeneic Hematopoietic Stem Cell Transplantation.Advances in experimental medicine and biology · 2023Review
- Immunology of cord blood T-cells favors augmented disease response during clinical pediatric stem cell transplantation for acute leukemia.Frontiers in pediatrics · 2023Review
- Assessment of the LOVO device for final harvest of novel cell therapies: a Production Assistance for Cellular Therapies multi-center study.Cytotherapy · 2022Article
- Trafficking and persistence of alloantigen-specific chimeric antigen receptor regulatory T cells in Cynomolgus macaque.Cell reports. Medicine · 2022Article
- Process development and validation of expanded regulatory T cells for prospective applications: an example of manufacturing a personalized advanced therapy medicinal product.Journal of translational medicine · 2022Article
- The emerging role of regulatory cell-based therapy in autoimmune disease.Frontiers in immunology · 2022Review
- Foxp3+ regulatory T cell therapy for tolerance in autoimmunity and solid organ transplantation.Frontiers in immunology · 2022Review
- The National Heart, Lung, and Blood Institute-funded Production Assistance for Cellular Therapies (PACT) program: Eighteen years of cell therapy.Clinical and translational science · 2021Review
- Multiply restimulated human thymic regulatory T cells express distinct signature regulatory T-cell transcription factors without evidence of exhaustion.Cytotherapy · 2021Article
- Genetic engineering of T cells for immunotherapy.Nature reviews. Genetics · 2021Review
- Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naive T Cells.Cell reports · 2021Article
- GMP-Compliant Universal Antigen Presenting Cells (uAPC) Promote the Metabolic Fitness and Antitumor Activity of Armored Cord Blood CAR-NK Cells.Frontiers in immunology · 2021Article
- [Genetically modified regulatory T cells: therapeutic concepts and regulatory aspects].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2020Review
- Umbilical Cord Blood Transplants: Current Status and Evolving Therapies.Frontiers in pediatrics · 2020Review
- Cryopreservation timing is a critical process parameter in a thymic regulatory T-cell therapy manufacturing protocol.Cytotherapy · 2019Article
- Regulatory T cells from patients with end-stage organ disease can be isolated, expanded and cryopreserved according good manufacturing practice improving their function.Journal of translational medicine · 2019Article
- Methods to manufacture regulatory T cells for cell therapy.Clinical and experimental immunology · 2019Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND
aimsThymic-derived regulatory T cells (tTreg) are critical regulators of the immune system. Adoptive tTreg transfer is a curative therapy for murine models of autoimmunity, graft rejection, and graft-versus-host disease (GVHD). We previously completed a "first-in-human" clinical trial using in vitro expanded umbilical cord blood (UCB)-derived tTreg to prevent GVHD in patients undergoing UCB hematopoietic stem cell transplantation (HSCT). tTreg were safe and demonstrated clinical efficacy, but low yield prevented further dose escalation.
methodsTo optimize yield, we investigated the use of KT64/86 artificial antigen presenting cells (aAPCs) to expand tTreg and incorporated a single re-stimulation after day 12 in expansion culture.
resultsaAPCs increased UCB tTreg expansion greater than eightfold over CD3/28 stimulation. Re-stimulation with aAPCs increased UCB tTreg expansion an additional 20- to 30-fold. Re-stimulated human UCB tTreg ameliorated GVHD disease in a xenogeneic model. Following current Good Manufacturing Practice (cGMP) validation, a trial was conducted with tTreg. tTreg doses up to >30-fold higher compared with that obtained with anti-CD3/28 mAb coated-bead expansion and Foxp3 expression was stable during in vitro expansion and following transfer to patients. Increased expansion did not result in a senescent phenotype and GVHD was significantly reduced. DISCUSSION: Expansion culture with cGMP aAPCs and re-stimulation reproducibly generates sufficient numbers of UCB tTreg that exceeds the numbers of T effector cells in an UCB graft. The methodology supports future tTreg banking and is adaptable to tTreg expansion from HSC sources. Furthermore, because human leukocyte antigen matching is not required, allogeneic UCB tTreg may be a useful strategy for prevention of organ rejection and autoimmune disease.
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Registered trials
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.