ArticleThe Journal of clinical investigation2024
A humanized IL-2 mutein expands Tregs and prolongs transplant survival in preclinical models.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Selective impact on regulatory T cells with sustained functional phenotypes by the interleukin-2 mutein VIS171 in a nonhuman primate model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- IL-2 mutein promotes antigen-specific transplant acceptance in mice through expansion of ST2Nature communications · 2026Article
- Decoding TNF receptor superfamily control of CD4Cell communication and signaling : CCS · 2026Review
- Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Long-term vagus nerve stimulation synergized with rapamycin elicits neuroimmune modulation to prolong skin allograft survival.iScience · 2026Article
- Regulatory T cell therapy in solid organ transplantation: mechanisms, translational progress, and remaining barriers.Frontiers in immunology · 2026Review
- Miniaturized IL-2/anti-IL-2 immunocytokines selectively activate and support theFrontiers in immunology · 2026Article
- Article
- Cellular Therapies in Transplantation - Regulatory T Cell Therapies and Virus Specific Therapies.Current transplantation reports · 2025Article
- Inborn errors of regulatory T-cell differentiation and function.The Journal of allergy and clinical immunology · 2025Review
- Article
- Regulatory T cell therapy in autoimmune liver disease and transplantation.JHEP reports : innovation in hepatology · 2025Review
- Understanding Immune Dynamics in Liver Transplant Through Mathematical Modeling.Bulletin of mathematical biology · 2025Article
- Revolutionizing Allogeneic Graft Tolerance Through Chimeric Antigen Receptor-T Regulatory Cells.Biomedicines · 2025Review
- Article
- De-coupling immune parameters and toxicity associated with IL-12 agonism.Cell reports · 2025Article
- Cytokines in transplantation tolerance.Best practice & research. Clinical haematology · 2025Review
- Tolerogenic Therapies in Cardiac Transplantation.International journal of molecular sciences · 2025Review
- Research Progress on Th17/Treg Cell Imbalance in Epileptic Seizures.Journal of inflammation research · 2025Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Long-term organ transplant survival remains suboptimal, and life-long immunosuppression predisposes transplant recipients to an increased risk of infection, malignancy, and kidney toxicity. Promoting the regulatory arm of the immune system by expanding Tregs may allow immunosuppression minimization and improve long-term graft outcomes. While low-dose IL-2 treatment can expand Tregs, it has a short half-life and off-target expansion of NK and effector T cells, limiting its clinical applicability. Here, we designed a humanized mutein IL-2 with high Treg selectivity and a prolonged half-life due to the fusion of an Fc domain, which we termed mIL-2. We showed selective and sustainable Treg expansion by mIL-2 in 2 murine models of skin transplantation. This expansion led to donor-specific tolerance through robust increases in polyclonal and antigen-specific Tregs, along with enhanced Treg-suppressive function. We also showed that Treg expansion by mIL-2 could overcome the failure of calcineurin inhibitors or costimulation blockade to prolong the survival of major-mismatched skin grafts. Validating its translational potential, mIL-2 induced a selective and sustainable in vivo Treg expansion in cynomolgus monkeys and showed selectivity for human Tregs in vitro and in a humanized mouse model. This work demonstrated that mIL-2 can enhance immune regulation and promote long-term allograft survival, potentially minimizing immunosuppression.
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What OpenQuestion holds
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.