For more than 20 years, BRI President Jane Buckner, MD, has explored a question that could change the way we treat autoimmune diseases: Can we turn the cells that cause disease into cells that protect us from disease? 

Many existing autoimmune disease treatments slow down the entire immune system, leaving a person vulnerable to infections and cancer. But this type of treatment would be highly targeted, only slowing down the specific cells that cause disease. 

“Developing this type of therapy has been a goal for most of my career,” Dr. Buckner said. “And the first clinical trial for type 1 diabetes (T1D) of the therapy we helped create has just begun.”

Laying the Groundwork

Before scientists can develop new medicines, they need to know why a disease happens in the first place. This new T1D treatment is based on decades of lab research examining the cells and processes that cause T1D. Early research from BRI’s Buckner, Long, Ziegler and Campbell labs helped improve our understanding of a few key players in the immune system: 

• Effector T cells, which help your body fight off germs
• Regulatory T cells (Tregs), which tell effector T cells to stop attacking when a germ is gone

T1D happens when effector T cells mistakenly attack the pancreas and the Tregs are unable to stop them from destroying the pancreatic beta cells that produce insulin. 

In the early 2000s, Dr. Buckner and her team started investigating what goes wrong with effector T cells and Tregs in T1D. They discovered that Tregs tell effector T cells to stop attacking — but effector T cells don’t listen. 

That finding led to a series of studies asking whether it was possible to create Tregs that could curb that attack. Building on a revolutionary approach that reprograms T cells to attack cancer, Dr. Buckner’s vision was to do the opposite in autoimmune diseases: Turn effector T cells into Tregs, so they stop attacking.

In partnership with David Rawlings, MD, at Seattle Children’s Research Institute, the research team used gene editing to turn effector T cells in T1D into Tregs. Then came a series of tests using biorepository samples from people with T1D, which revealed that engineered Tregs could in fact curb the cells that cause T1D in the lab. These tests paved the way to use this approach in people.

BRI's Mission in Action

Now, this therapy is being tested in the POLARIS Study, sponsored by GentiBio. This study of adults recently diagnosed with T1D. The study will follow people for a year and a half and answer these questions: 

• Is the therapy safe?
• How does the therapy affect the body and immune system?
• Do people who take it continue producing insulin?

If the study finds the therapy to be safe and effective, the next step will be larger trials in more people and fine-tuning the dosage. Dr. Buckner and her team will study how long these treatments work for and how to make them widely accessible. 

“My hope is that we can rapidly invest in making this therapy relatively inexpensive, easy to administer and available to everyone who needs it,” Dr. Buckner said.

Harnessing the power of Tregs doesn’t stop with T1D: Dr. Buckner’s team has already developed Tregs that could target the joints in rheumatoid arthritis and the liver in a rare autoimmune disease called primary biliary cholangitis. This type of therapy holds the promise to work for many other autoimmune diseases and allergies too.

“We started by understanding the fundamental biology and built on that knowledge to inform better care,” Dr. Buckner said. “This is what BRI exists to do and it’s a significant step toward our vision of a healthy immune system for everyone.”