Even for a newly minted Nobel laureate, downtime is hard to find. Just a few weeks after winning the 2025 Nobel Prize in Physiology or Medicine for his discovery of regulatory T cells or Tregs, immunologist Shimon Sakaguchi, M.D., Ph.D., and colleagues have published two new papers demonstrating how rogue T cells can be converted into Tregs to treat a suite of autoimmune diseases.
Both papers were published in Science Translational Medicine on Oct. 22.
Tregs are a rare type of T cell that patrol the body for other T cells that have become autoreactive, meaning they attack the body itself. By pruning these rogue T cells, Tregs help protect against autoimmune diseases in a process called peripheral immune tolerance.
In their first paper, Sakaguchi’s team extracted T cells from mice and exposed them to a small molecule that activated a gene called Foxp3. Foxp3 is critical for the development of Tregs, and the elucidation of its role is part of what earned Sakaguchi and fellow 2025 laureates Mary Brunkow, Ph.D., and Fred Ramsdell, Ph.D., the Nobel Prize.
At the same time, Sakaguchi told Fierce Biotech, the team blocked stimulation of the CD28 receptor, which further promoted the expression of Foxp3 and other genes important for Tregs. CD28 normally helps activate T cells to produce an immune response, so shutting it down allows the cells to instead take up the regulatory role played by Tregs.
“Both procedures together can convert antigen-specific or disease-specific T cells into Tregs that specifically suppress the disease mediated by the effector T cells,” Sakaguchi said. In other words, the very same T cells causing the disease can be flipped into their own treatment.
In the first paper, the researchers used the converted Tregs to suppress inflammation in mice with inflammatory bowel disease and graft-versus-host disease. In the second paper, the team adapted the procedure to treat mice with the autoimmune disease pemphigus vulgaris.
Also in the first paper, Sakaguchi’s team successfully used its small molecule approach to switch human T cells into Tregs in the lab. A company spun out of Sakaguchi’s lab at Osaka University, RegCell, next plans to conduct first-in-human trials of the technique, the Nobel laureate told Fierce.
RegCell is far from the only company trying to engineer Tregs for therapeutic uses and isn’t even the only one backed by Nobel knowledge. Sakaguchi’s fellow laureate Ramsdell is a co-founder of Sonoma Biotherapeutics and currently serves the company as scientific advisor, after previously holding the title of chief scientific officer.
SonomaBio’s technique is to extract Tregs and modify their genomes to express a chimeric antigen receptor, or CAR, targeting citrullinated vimentin, a protein associated with inflammation in rheumatoid arthritis, and other citrullinated proteins. The biotech plans to present phase 1 data demonstrating the cell therapy’s safety and early signs of efficacy at the upcoming American College of Rheumatology conference in Chicago.
Unlike SonomaBio, “we do not manipulate the genome,” Sakaguchi said. “We can convert disease-mediating T cells into Tregs simply by targeting signaling pathways, not the genome.”
Sakaguchi is also a longtime advisor to Coya Therapeutics, a biotech developing self-administered biologics to boost Treg activity inside patients’ bodies for treatment of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Coya’s lead asset COYA 302 is furthest along in ALS, with the biotech currently testing the asset in a phase 2 trial that launched last month after a delay from the FDA.