ArticleBlood2023
Prevention of acute GVHD using an orthogonal IL-2/IL-2Rβ system to selectively expand regulatory T cells in vivo.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- CD4Communications biology · 2026Article
- Regulatory T cell approaches for graft-versus-host disease prevention.Current opinion in immunology · 2026Review
- Thirty years in, regulatory T cells are ready for medicine.Frontiers in immunology · 2026Review
- Regulatory T cells in the era of cell and gene therapy: biology, clinical translation, and future prospects.Frontiers in immunology · 2026Review
- Review
- Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Interleukin Networks in GVHD: Mechanistic Crosstalk, Therapeutic Targeting, and Emerging Paradigms.International journal of molecular sciences · 2025Review
- Regulatory T cell therapy for Graft-versus-Host Disease.Bone marrow transplantation · 2025Review
- Harnessing the biology of regulatory T cells to treat disease.Nature reviews. Drug discovery · 2025Review
- A higher ratio of IL-2/IL-4 may be an early predictor of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2025Article
- Graft-Versus-Host Disease Mouse Models: A Clinical-Translational Perspective.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Cytokine Couture: Designer IL2 Molecules for the Treatment of Disease.ImmunoTargets and therapy · 2025Review
- Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions.Signal transduction and targeted therapy · 2024Review
- Role of FoxP3Human gene therapy · 2024Review
- Challenges and strategies in relation to effective CAR-T cell immunotherapy for solid tumors.Medical oncology (Northwood, London, England) · 2024Review
- Genetic engineering of regulatory T cells for treatment of autoimmune disorders including type 1 diabetes.Diabetologia · 2024Review
- Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- A systematic literature review of 74 Chinese blastic plasmacytoid dendritic cell neoplasm patients.Therapeutic advances in hematology · 2024Review
- Treg-targeted IL-2/anti-IL-2 complex controls graft-Haematologica · 2024Article
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with hematological disorders and bone marrow (BM) failure syndromes. Graft-versus-host disease (GVHD) remains a leading cause of morbidity posttransplant. Regulatory T cell (Treg) therapies are efficacious in ameliorating GVHD but limited by variable suppressive capacities and the need for a high therapeutic dose. Here, we sought to expand Treg in vivo by expressing an orthogonal interleukin 2 receptor β (oIL-2Rβ) that would selectively interact with oIL-2 cytokine and not wild-type (WT) IL-2. To test whether the orthogonal system would preferentially drive donor Treg expansion, we used a murine major histocompatibility complex-disparate GVHD model of lethally irradiated BALB/c mice given T cell-depleted BM from C57BL/6 (B6) mice alone or together with B6Foxp3+GFP+ Treg or oIL-2Rβ-transduced Treg at low cell numbers that typically do not control GVHD with WT Treg. On day 2, B6 activated T cells (Tcons) were injected to induce GVHD. Recipients were treated with phosphate-buffered saline (PBS) or oIL-2 daily for 14 days, then 3 times weekly for an additional 14 days. Mice treated with oIL-2Rβ Treg and oIL-2 compared with those treated with PBS had enhanced GVHD survival, in vivo selective expansion of Tregs, and greater suppression of Tcon expansion in secondary lymphoid organs and intestines. Importantly, oIL-2Rβ Treg maintained graft-versus-tumor (GVT) responses in 2 distinct tumor models (A20 and MLL-AF9). These data demonstrate a novel approach to enhance the efficacy of Treg therapy in allo-HSCT using an oIL-2/oIL-2Rβ system that allows for selective in vivo expansion of Treg leading to GVHD protection and GVT maintenance.
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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.