ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
CAR- and TRuC-redirected regulatory T cells differ in capacity to control adaptive immunity to FVIII.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- Review
- The Role of Chimeric Antigen Receptor Regulatory T Cells in Promoting Immune Tolerance in Solid Organ Transplantation:Saudi medical journal · 2026Review
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- Cellular Therapies in Transplantation - Regulatory T Cell Therapies and Virus Specific Therapies.Current transplantation reports · 2025Article
- CAR-engineered cytolytic Tregs reverse pulmonary fibrosis and remodel the fibrotic niche with limited CRS.JCI insight · 2025Article
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- Review
- Armored human CAR TScience advances · 2025Article
- An engineered Treg selective immunocytokine induces sustained immune modulation in a preclinical model of hemophilia A.Journal of thrombosis and haemostasis : JTH · 2025Article
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Expanding the engineered Treg multiverse.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene editing of CD3 epsilon to redirect regulatory T cells for adoptive T cell transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- Harnessing the biology of regulatory T cells to treat disease.Nature reviews. Drug discovery · 2025Review
- Generation of Human Chimeric Antigen Receptor Regulatory T Cells.Journal of visualized experiments : JoVE · 2025Article
- CXCR5 engineered human and murine Tregs for targeted suppression in secondary and tertiary lymphoid organs.Frontiers in immunology · 2025Article
- Editorial: Repurposing cancer immunotherapies for use in autoimmunity and transplantation.Frontiers in immunology · 2025Article
- Chimeric antigen receptor T cell therapy for autoimmune disease.Nature reviews. Immunology · 2024Review
- Role of FoxP3Human gene therapy · 2024Review
- Selective targeting or reprogramming of intra-tumoral Tregs.Medical oncology (Northwood, London, England) · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Regulatory T cells (Tregs) control immune responses in autoimmune disease, transplantation, and enable antigen-specific tolerance induction in protein-replacement therapies. Tregs can exert a broad array of suppressive functions through their T cell receptor (TCR) in a tissue-directed and antigen-specific manner. This capacity can now be harnessed for tolerance induction by "redirecting" polyclonal Tregs to overcome low inherent precursor frequencies and simultaneously augment suppressive functions. With the use of hemophilia A as a model, we sought to engineer antigen-specific Tregs to suppress antibody formation against the soluble therapeutic protein factor (F)VIII in a major histocompatibility complex (MHC)-independent fashion. Surprisingly, high-affinity chimeric antigen receptor (CAR)-Treg engagement induced a robust effector phenotype that was distinct from the activation signature observed for endogenous thymic Tregs, which resulted in the loss of suppressive activity. Targeted mutations in the CD3ζ or CD28 signaling motifs or interleukin (IL)-10 overexpression were not sufficient to restore tolerance. In contrast, complexing TCR-based signaling with single-chain variable fragment (scFv) recognition to generate TCR fusion construct (TRuC)-Tregs delivered controlled antigen-specific signaling via engagement of the entire TCR complex, thereby directing functional suppression of the FVIII-specific antibody response. These data suggest that cellular therapies employing engineered receptor Tregs will require regulation of activation thresholds to maintain optimal suppressive function.
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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.