While presenting this year’s Nobel Prize in Physiology or Medicine to three immunologists who discovered and characterized regulatory T cells, committee chair Olle Kämpe, M.D., Ph.D., told the assembled crowd that, like last year’s prize for microRNA, the award-winning science is still a ways off from translating into new medicines.
“This year’s Nobel laureates get the prize for discovering a principle,” Kämpe said. “There is quite a lot of development going on, but it’s still early.”
While it’s true that there are no approved medicines using regulatory T cells, also known as Tregs, these immune peacekeepers are actually much closer to realization than Kämpe’s words might suggest.
“The field is pretty advanced in some aspects and still needs validation in others,” Jeff Bluestone, Ph.D., CEO of Sonoma Biotherapeutics, told Fierce Biotech. “The field has moved very, very fast in recent years and there's a lot of opportunity here that's being realized.”
Bluestone co-founded SonomaBio with Fred Ramsdell, Ph.D., one of this year’s Nobel laureates. Ramsdell previously served as the biotech’s chief scientific officer and is now a scientific advisor.
As an example of an advanced Treg application, Bluestone pointed to Bay Area-based Orca Bio’s Orca-T cell therapy, which contains a cocktail of Tregs, stem cells and other T cells and is currently pending approval with the FDA for use in blood diseases like leukemia. A decision from the agency is expected by April 6, 2026.
During the Nobel Prize announcement, Thomas Perlmann, Ph.D., secretary-general of the Nobel Assembly, said that there are more than 200 active clinical trials harnessing Tregs.
SonomaBio itself is on the cusp of presenting phase 1 Treg cell therapy data at the American College of Rheumatology conference, which meets from Oct. 24-29 in Chicago.
“It’s not that these things are not close to impacting people,” Bluestone said. “They absolutely are.”
Nobel beginnings
Tregs are unofficially known as “the police“ or “the peacekeepers“ of the immune system. They exist in low numbers throughout the body and patrol for T cells that have gone haywire and begun attacking the body itself. In this way, Tregs protect against the development of autoimmune diseases like lupus, rheumatoid arthritis and more, in a process called peripheral immune tolerance.
Tregs were discovered in 1995 by one of 2025’s new Nobel laureates, Shimon Sakaguchi, M.D., Ph.D., who was then at the Aichi Cancer Center in Nagoya, Japan. He discovered a population of T cells expressing the interleukin-2 receptor alpha chain (known as CD25) that protected mice from autoimmunity. Sakaguchi is now a professor at Japan's Osaka University.
The other two freshly chosen Nobel winners, Ramsdell and Mary Brunkow, Ph.D., identified in 2001 that a gene called Foxp3 was essential for Tregs to develop. Sakaguchi confirmed Foxp3’s role in 2003, and with that, a new field of Treg biology was born.
Brunkow is now a senior program manager at the Institute for Systems Biology (ISB) in Seattle, where she oversees projects studying the complicated genetics of diseases like Huntington’s disease, Alzheimer’s disease and bipolar disorder.
“Her work transformed how we think about the immune system,” ISB President Jim Heath, Ph.D., said about Brunkow in an Oct. 6 release.
As for Sakaguchi’s work, studying Foxp3 had previously been “kind of a sidebar” to most immunologists, Ramsdell told Fierce Biotech in an interview.
“Now we could explain everything he was seeing, and we now had a molecular tool with which to further explore these cells [and] understand what they do," Ramsdell said.
It didn’t take long for scientists to recognize the therapeutic potential of cells that can tamp down autoimmune responses. SonomaBio’s Bluestone published his first Treg paper in 2000—before Foxp3 was identified—and in the same year, he joined the faculty of the University of California, San Francisco. From there, he was off to the races.
“We very rapidly said, ‘Could we make Tregs into a cell therapy effort?’” Bluestone said. His team began studying Tregs in humans starting in 2006, identifying other distinguishing marks on the rare cells and figuring out how to isolate them from patients with diabetes.
In 2015, Bluestone led a small clinical trial to isolate and grow Tregs from diabetes patients and then reinfuse the cells back into them. The results, published in Science Translational Medicine, confirmed that Treg cell therapy was safe and a potentially promising treatment for autoimmune diseases like diabetes.
Bluestone’s UCSF team ran “probably a dozen trials,” he said, on everything from kidney transplants to pemphigus to COVID-19. “The challenge was that it's very hard to do this in an academic setting. The studies were very small.”
To scale up his Treg work into potential therapies, Bluestone, Ramsdell and fellow Treg pioneers Alexander Rudensky, Ph.D., and Qizhi Tang, Ph.D., created SonomaBio in 2019.
SonomaBio’s lead Treg cell therapy is SBT-77-7101, which is currently in development for rheumatoid arthritis (RA) and hidradenitis suppurativa, with arthritis being the biotech’s primary focus. In RA, the patient’s immune system attacks their own joints, causing chronic swelling, stiffness, pain and mobility issues.
In its upcoming ACR presentations, SonomaBio will share data from six patients with RA who received the Treg therapy. Thus far, the company has seen no dose-limiting toxicities, neurotoxicity or cytokine release syndrome, according to one of the presentation’s abstracts. In addition, swelling and tenderness in the patients’ joints dropped after treatment.
“These are patients that have highly refractory disease where they have failed many, many different therapies,” Bluestone said. “In the majority of the individuals treated, there has been a significant reduction in disease activity.”
SonomaBio’s cell therapy uses Tregs extracted from patients, which are then genetically modified to express a chimeric antigen receptor (CAR) that targets citrullinated vimentin, a protein associated with inflammation in RA. When reintroduced, this engineered Treg army is meant to head to the joints to quell the autoimmune response causing the inflammation.
“It's a simple genetic modification to a cell, if any genetic modification can be described as simple,” Ramsdell said. “By giving these cells the right signals in the right places, they will engage their natural function, and that we believe will lead to inhibition of this inflammation and probably also start a tissue repair process.”
SonomaBio’s Treg technique has been endorsed by Regeneron, which inked a $120 million preclinical collab with the biotech in 2023.
SonomaBio isn't the only Treg biotech benefiting from Nobel wisdom. Houston-based Coya Therapeutics boasts Sakaguchi as a scientific advisor and is pursuing a pipeline of Treg assets outside the scope of autoimmune diseases.
“Dr. Sakaguchi has been with us as a scientific advisor since our formative days,” Coya CEO Arun Swaminathan, Ph.D., told Fierce Biotech. “Everybody at the company is brimming with pride.”
Coya is seeking to weaponize Tregs against disease without ever taking the cells out of the patient’s body. The biotech’s lead asset, COYA 302, combines a low dose of interleukin-2—which activates Tregs—and a CTLA-4 antibody to help suppress inflammation.
The activated Tregs hit the brakes on inflammation, Swaminathan said, while the anti-inflammatory boost helps the regulatory cells stay active for longer.
COYA 302 is furthest along in ALS, with Coya currently testing the asset in a phase 2 trial that launched last month after a delay from the FDA. Coya’s work is based on the research of Stanley Appel, M.D., who has long studied the role Tregs play in brain inflammation and neurodegeneration; Appel, a neurologist at Houston Methodist, conducted a small phase 1 trial of Treg cell therapy in ALS in 2018.
ALS “is one of the most inflammatory neurodegenerative diseases,” Coya’s Swaminathan said. “There's a direct correlation between Treg dysfunction and how fast and how poorly these ALS patients do.”
The CEO’s hope is that COYA 302 can become a self-administered injection, similar to GLP-1 drugs like Ozempic, which patients or their caretakers can administer once or twice a month.
“It's going to be a more convenient administration for patients,” Swaminathan said, “as opposed to cell therapies.”
The biotech also plans to pursue COYA 302 in frontotemporal dementia, with hopes to file an investigational new drug application for a phase 2 trial in the first half of next year, according to Swaminathan. With other preclinical Treg assets, the biotech plans to go after Alzheimer’s and Parkinson’s disease, which both feature neuroinflammation as part of their pathology.
“Nerve cells are getting damaged and it's causing a pretty inflammatory environment, and it becomes a vicious circle,” Swaminathan said. “Addressing neuroinflammation is the key to stopping these diseases.”
A fertile field
While Tregs are most famous for their role in stopping autoimmunity, Coya’s work shows the broader potential of these suppressive cells. Ramsdell, Bluestone and Swaminathan all agree that Tregs could treat just about any disease caused by inflammation.
“I think the best answer is that these things become a universal drug,” Ramsdell said. An off-the-shelf Treg therapy could, in theory, be tuned to target any disease-ridden tissue and even engineered to directly support tissue repair. “If you could do this in a universal manner, then I think you could address an enormous number of inflammatory diseases.”
A Treg-based inflammatory panacea is a long way off, but the biotech community has been working diligently over the last couple of decades to leverage the cells’ power against a range of diseases.
London-based Quell Therapeutics is also developing Treg cell therapies for autoimmune diseases, as well as other inflammatory conditions and organ transplants, with a phase 2 liver transplant trial ongoing. Others like TRexBio and GentiBio have also reached the clinic with their Treg-based autoimmune candidates. And Georgiamune, a 2025 Fierce 15 honoree, also boasts Ramsdell as a scientific advisor and has three Treg-targeting candidates in the clinic.
Instead of using Tregs as an ally, others still are trying to silence the regulators themselves in order to unshackle the immune system and boost the body’s ability to fight cancer. Some T cell receptors that are being targeted to inhibit Treg function include TIGIT, LAG-3 and the aforementioned CTLA-4.
“There's a lot of really interesting science being done here, and I suspect that you'll see a number of advances in the cancer space by lots of different companies,” said SonomaBio’s Bluestone, who has himself studied the therapeutic potential of reducing Treg activity in liver metastases.
With all of the industry activity around Tregs, along with the fact that Ramsdell and Brunkow conducted their Nobel-winning work at British biotech Celltech (acquired by UCB), it can be easy to forget that public science funding played a key role in launching Treg biology as well. The mouse model studied by Ramsdell and Brunkow, called scurfy, was developed by a long-running mammalian genetics program at Oak Ridge National Laboratory in Tennessee.
“Without the U.S. government having the foresight in the 1940s to try to study the effect of ionizing radiation on mammals, this discovery wouldn't exist,” Ramsdell said. “Biomedical research has benefited immeasurably from public support over the years, myself included, and I think everyone in this field is incredibly grateful for that. And I think to stay at that level is something that we should aspire to.”