Can Treg Cell Therapy Really Target Autoimmunity?
•February 17, 2026
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Why It Matters
Successful early data validates Treg cell therapy as a viable precision‑immunotherapy for autoimmune diseases, potentially reshaping treatment paradigms and attracting significant investment.
Key Takeaways
- •Sonoma's CAR‑Treg SBT‑77‑7101 cuts joint swelling 67%
- •Coya's COYA 301 combines low‑dose IL‑2 and CTLA‑4 Ig
- •Quell pivots from liver‑reject QEL‑001 to rheumatoid arthritis QEL‑005
- •Zag Bio targets thymus to expand tolerogenic Tregs
- •RegCell reports durable Treg reprogramming in IBD models
Pulse Analysis
The resurgence of regulatory T‑cell research, sparked by Shimon Sakaguchi’s 1995 discovery of FOXP3‑dependent Tregs, has matured into a multi‑billion‑dollar immunotherapy niche. Investors now view Treg platforms as a logical extension of CAR‑T technology, offering the promise of antigen‑specific immune modulation without the cytotoxicity of conventional CAR‑T cells. This shift aligns with broader industry trends toward cell‑based precision medicines that address chronic inflammation and autoimmunity, markets projected to exceed $150 billion by 2030.
Recent clinical readouts underscore the field’s momentum. Sonoma’s SBT‑77‑7101 demonstrated a 67% reduction in joint swelling and robust protein depletion in a Phase 1 rheumatoid‑arthritis cohort, confirming that engineered CAR‑Tregs can home to inflamed tissue and exert durable suppression. Meanwhile, Coya’s COYA 301, a skin‑applied IL‑2/CTLA‑4 Ig cocktail, earned IND clearance for ALS, highlighting the diversification of delivery modalities beyond intravenous infusion. Quell’s strategic pivot away from liver‑transplant rejection toward rheumatoid arthritis and systemic sclerosis reflects a pragmatic focus on indications with clearer regulatory pathways and larger patient populations.
Despite encouraging data, challenges remain. Manufacturing autologous Treg products at scale, ensuring phenotypic stability, and navigating complex FDA expectations for cell‑based therapies demand substantial capital and technical expertise. Companies such as RegCell and Zag Bio are exploring allogeneic and thymic‑targeted approaches to mitigate these hurdles, potentially lowering costs and broadening access. As the pipeline matures, the next few years will likely determine which platforms achieve commercial viability, setting the stage for a new class of immune‑tolerant therapeutics that could redefine treatment standards across autoimmune and transplant medicine.
Can Treg cell therapy really target autoimmunity?
Regulatory T cells, better known as Tregs, are emerging as one of the most promising frontiers in modern immunotherapy. Once viewed simply as the immune system’s peacekeepers, these specialized cells are now being engineered as therapies to regulate an immune system that has gone rogue. From autoimmune diseases like type 1 diabetes to inflammatory conditions such as multiple sclerosis, and even in preventing organ transplant rejection, Treg cell therapies are rethinking what precision medicine could look like.
Treg cells: a discovery like no other
Without Tregs, the immune system might react excessively, which could cause the body to attack its own cells. This may lead to autoimmune disease. In these cases, it is often best if the immune system doesn’t respond. Tregs know when to and when not to respond.
These cells were discovered more than three decades ago by Japanese immunologist and professor at Osaka University, Shimon Sakaguchi, who was swimming against the tide at the time, as researchers back then were convinced that immune tolerance solely came about from harmful immune cells that were eliminated in the thymus, an organ near the chest that defends the body against infections. With Sakaguchi’s unearthing of Treg cells, it became clear that the immune system is more complex than previously thought.
Following Sakaguchi’s discovery, American immunologists Mary Brunkow and Fred Ramsdell made another key finding. They found a mutation in the gene Foxp3, which they first identified in mice, that was linked to the development of an autoimmune condition called autoimmune polyendocrine syndromes that causes early‑onset autoimmunity in children.
Then, Sakaguchi proved that the Foxp3 gene controls the cells that he discovered, the Treg cells, linking their dysfunction to the development of autoimmune diseases.
The three scientists were awarded the Nobel Prize in Physiology or Medicine in October last year for their discoveries. Ramsdell had gone on to co‑found Sonoma Biotherapeutics in California, along with fellow scientists researching the potential of Treg cells.
“The discovery of the gene, FOXP3, changed our understanding of peripheral tolerance and led to a new field of immunotherapy,” said Jeff Bluestone, chief executive officer (CEO) and president of Sonoma.
Sonoma’s Treg cell therapy SBT‑77‑7101 reduces swelling in rheumatoid arthritis
This “new field” has been the focus of various biotechs today, Sonoma being one of them. Regarding them as “sentinels” that detect and suppress immune responses that are uncalled for, Sonoma has developed the therapeutic candidate SBT‑77‑7101. It is a chimeric antigen receptor (CAR) Treg therapy designed to treat autoimmune conditions such as rheumatoid arthritis and hidradenitis suppurativa, a chronic skin disease.
When the immune system attacks the joints in rheumatoid arthritis, it causes painful swelling and stiffness around the joints. SBT‑77‑7101 targets disease‑causing proteins in the inflamed areas to dampen inflammation. The candidate, which is in phase 1 trials at present, demonstrated deeper reductions in joint counts—a measure of inflammation in arthritis—in people who received a higher dosage of the drug versus the lower‑dosage cohort.
Around 67 % of patients saw swelling decline by half and 83 % had a depletion of the harmful proteins. The drug was found to be safe, according to the trial data.
“It is gratifying to see the preliminary safety, pharmacokinetic/pharmacodynamic (PK/PD), and efficacy data in the phase 1 REGULATE‑RA clinical trial, as it validates the potential for antigen‑directed Tregs to treat autoimmunity, even in highly refractory patients with high levels of baseline disease,” said Joe Arron, chief scientific officer (CSO) of Sonoma Biotherapeutics.
“In addition, to do so without the need for conditioning chemotherapy further supports the approach we have pioneered here at SonomaBio as we work to develop a new generation of targeted and durable Treg cell therapies.”
Coya Therapeutics’ COYA 301 nabs IND approval
Mary Brunkow is currently involved in human genetics research at the Institute for Systems Biology in Seattle, and Shimon Sakaguchi serves as a scientific advisor to Texas‑based Treg cell‑treatment developer Coya Therapeutics. The biotech has been through rocky times since it went public for $15 million in late 2022. Its pipeline differs from typical Treg cell therapies; Coya’s candidates are described as “Treg‑enhancing” therapies.
Aimed at targeting Treg cell dysfunction, Coya’s Treg‑enhancing therapy COYA 301 is administered through the skin and heightens the anti‑inflammatory properties of Treg cells so that they can suppress inflammation activated by immune cells. The candidate combines low‑dose IL‑2 and CTLA‑4 Ig to address the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS).
After a delayed IND application, Coya received FDA approval in August and began phase 2 studies in September. Top‑line results are expected in 2026, positioning Coya as a pioneer in the neuroscience space by targeting neuroinflammation through immune‑cell modulation.
In addition to his advisory role at Coya, Sakaguchi founded the California‑headquartered Osaka University spinoff RegCell. RegCell’s research and development is grounded in Sakaguchi’s work, including a Treg cell therapeutics platform to deliver cell therapies that combat autoimmunity.
Following a $45.8 million funding round a year ago, RegCell recently published two peer‑reviewed papers showing that T cells reprogrammed into Treg cells “achieved long‑lasting immune regulation in models of inflammatory bowel disease and graft‑versus‑host disease.” Similar results were observed in mouse models of pemphigus vulgaris, a rare severe autoimmune disease that causes painful, fragile blisters on the skin. The Treg cells suppressed autoimmune responses without impairing normal immune function.
Quell Therapeutics ditches one Treg cell therapy, switches focus to another
London‑based Quell Therapeutics is among the most advanced companies in the clinic and has collaborated with AstraZeneca in an $85 million deal to develop two CAR‑Treg therapies for type 1 diabetes and inflammatory bowel disease (IBD), both currently in IND‑enabling stages.
However, Quell recently halted its phase 1/2 trial of QEL‑001, which was testing organ‑rejection prevention in liver‑transplant patients, and shifted focus to QEL‑005, a candidate slated to enter the clinic for rheumatoid arthritis and systemic sclerosis.
Quell’s approach, dubbed “chill not kill,” uses engineered CAR‑Treg therapies that modulate rather than destroy immune cells, allowing the immune system to function normally while treating autoimmunity.
While Quell pivots, Bristol Myers Squibb‑backed Abata Therapeutics exited the therapeutic space late last year, closing its doors amid a challenging fundraising environment.
Conversely, Zag Bio emerged from stealth with an $80 million Series A round in October, introducing a novel method to deliver tolerizing antigens designed to induce immune tolerance rather than an immune reaction. Zag Bio creates antibodies that target the thymus, expanding Treg cells and depleting detrimental immune cells. The thymic Tregs then migrate to diseased tissues to control inflammation. Its lead candidate ZAG‑101 is currently in preclinical trials for type 1 diabetes.
Outlook
As Treg cell therapies comprise various approaches—illustrated by Quell, Sonoma, RegCell, and others—the overarching goal remains the same: to curb inflammation and treat autoimmunity. With the field advancing toward and into the clinic, it may not be long before we see which strategies succeed and reach the market.
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