ArticleJCI insight2024
GNTI-122: an autologous antigen-specific engineered Treg cell therapy for type 1 diabetes.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 41 citations in OpenAlex.
- Receptor-tethered orthogonal IL-2 enhances regulatory T cell therapy.The Journal of experimental medicine · 2026Article
- T Cell Thoughts.Immunological reviews · 2026Review
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- A synthetic NKG2A engager enables long-term persistence of HLA-deficient allogeneic engineered Tregs.EMBO molecular medicine · 2026Article
- Reducing Diabetic Ketoacidosis in Pediatric Type 1 Diabetes: The Impact of Screening Programs and Early Disease-Modifying Treatment.Journal of clinical medicine · 2026Review
- Next-Generation regulatory T cell therapies: Translational considerations for inflammatory bowel disease.Human immunology · 2026Review
- Emerging therapies for type 1 diabetes: Immunotherapy and gene editing advances.The Journal of international medical research · 2026Review
- Clinical progress of engineered cellular immunotherapies for autoimmunity.Nature biotechnology · 2026Review
- Balancing immunity with Tregs.Nature biotechnology · 2026Article
- Artificial intelligence-driven therapeutics for disease modification in type 1 diabetes: a digital public health and clinical translation framework.Frontiers in public health · 2026Review
- The relativity of regulatory T cell suppression modes.Frontiers in immunology · 2026Review
- Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges.Frontiers in immunology · 2026Review
- Modulating immune response for the prevention and treatment of type 1 diabetes.Frontiers in immunology · 2026Review
- Automated GMP-compatible production of universal CAR Tregs for organ-targeted tolerance induction.Journal of translational medicine · 2025Article
- The Potential of β-Synuclein-Specific Regulatory T Cell Therapy as a Treatment for Progressive Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.Journal of hematology & oncology · 2025Review
- TCR-Based Antigen-Specific Therapy for Type 1 Diabetes Mellitus: From Editing Autoreactive Clones to Tolerance Induction.International journal of molecular sciences · 2025Review
- Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.International journal of molecular sciences · 2025Review
- HLA-A2 CAR/IL-2-CISC engineered Treg display robustMolecular therapy. Methods & clinical development · 2025Article
- Neighborhood enrichment for the identification of antigen-specific T-cell receptors.Briefings in bioinformatics · 2025Article
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tregs have the potential to establish long-term immune tolerance in patients recently diagnosed with type 1 diabetes (T1D) by preserving β cell function. Adoptive transfer of autologous thymic Tregs, although safe, exhibited limited efficacy in previous T1D clinical trials, likely reflecting a lack of tissue specificity, limited IL-2 signaling support, and in vivo plasticity of Tregs. Here, we report a cell engineering strategy using bulk CD4+ T cells to generate a Treg cell therapy (GNTI-122) that stably expresses FOXP3, targets the pancreas and draining lymph nodes, and incorporates a chemically inducible signaling complex (CISC). GNTI-122 cells maintained an expression profile consistent with Treg phenotype and function. Activation of CISC using rapamycin mediated concentration-dependent STAT5 phosphorylation and, in concert with T cell receptor engagement, promoted cell proliferation. In response to the cognate antigen, GNTI-122 exhibited direct and bystander suppression of polyclonal, islet-specific effector T cells from patients with T1D. In an adoptive transfer mouse model of T1D, a mouse engineered-Treg analog of GNTI-122 trafficked to the pancreas, decreased the severity of insulitis, and prevented progression to diabetes. Taken together, these findings demonstrate in vitro and in vivo activity and support further development of GNTI-122 as a potential treatment for T1D.
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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 Socratic graph.