Abstract IA08: Development and use of Engineered Regulatory T cells to treat Autoimmune Diseases
Bibliographic record
Abstract
Abstract Regulatory T (Treg) cells are critical for maintaining peripheral tolerance, preventing autoimmunity, and limiting chronic inflammatory diseases. This small CD4+CD25+CD127lo T cell population develops in the thymus and peripheral tissues through expression of the epigenetically stabilized transcription factor FOXP3. Tregs mediate their tolerogenic effects via multiple mechanisms, including secretion of inhibitory cytokines, IL-2 consumption to starve effector T cells, suppression of Teff cells through metabolic disruption, and modulation of antigen-presenting cell maturation and function. Collectively, these mechanisms broadly suppress immune cell activation and effector function. Additionally, Tregs can promote tissue repair, complementing their immunosuppressive effects. Recent advances have focused on harnessing Tregs as a therapeutic approach for autoimmune diseases, aiming to restore immune tolerance and repair tissue damage. A key to therapeutic success lies in developing a stable Treg product that preserves functional activity and lineage integrity under inflammatory conditions. Previous studies have shown that polyclonal Tregs can be administered safely to patients with a variety of autoimmune diseases. The cells can be detected in the circulation at least one year after administration and in small studies the cells have been shown to suppress inflammatory cytokines produced by effector T cells. In this presentation, I will highlight the differences between blood Tregs and the synovial microenvironment in the joints of healthy donors versus patients with Rheumatoid Arthritis (RA). Additionally, I will present early preclinical and clinical data on our first engineered product, SBT-77-7101, which expresses a citrullinated protein (CitP)-specific Chimeric Antigen Receptor (CAR) derived from a RA patient-specific anti-citrullinated protein antibody. These CitP CAR-Tregs retain stable phenotypic and epigenetic profiles, remain functional in inflammatory environments, recognize multiple citrullinated proteins present in diseased tissue, and are activated by synovial fluid from patients with RA. Clinical studies of SBT-77-7101 in patients with Rheumatoid Arthritis and Hidradenitis Suppurativa will be summarized. Finally, next-generation Treg engineering strategies aimed at enhancing Treg durability and specificity will be presented including approaches to maximize Treg stability via genome editing and develop synthetic FOXP3-dependent promoters to ensure controlled CAR expression. Citation Format: Jeffrey A Bluestone. Development and use of Engineered Regulatory T cells to treat Autoimmune Diseases [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr IA08.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".