Cellular therapies that originally were developed for cancer are now being studied by University of Colorado Department of Medicine faculty as what could be the next generation of treatments against rheumatoid arthritis, lupus, and other autoimmune diseases.
Melissa Griffith, MD, and Larry Moreland, MD – both faculty members in the Division of Rheumatology – are overseeing a series of trial studies into the use of genetically engineered immune cells extracted from the patient’s body in the fight against several autoimmune diseases.
“We think of these as living drugs that can harness people’s own immune system and try to right the ship,” says Griffith, an assistant professor.
In autoimmune diseases, the body’s immune system mistakenly detects healthy cells, tissues, and organs as being foreign and attacks them, causing inflammation. These diseases can affect almost any part of the body, and symptoms can be mild to severe. More than 15 million people in the U.S., about 4.6% of the population, have been diagnosed with at least one autoimmune disease, and 63% of them are women, a recent study says.
Existing treatments often involve powerful immunosuppressive drugs to manage or suppress these diseases, but they require repeated doses and generally do not produce sustained, drug-free remission.
“Rheumatoid arthritis is the most common autoimmune disease we see,” says Moreland, a professor and director of the CU Interdisciplinary Joint Biology Program. “A lot of therapies – biologics and targeted therapies – are on the market. However, there’s still an unmet need. A significant percentage of patients are difficult to treat or don’t respond to treatment. So we’re looking for ways to add to our toolbox.”
Other autoimmune diseases “are rare, but they can affect a wide range of ages of patients,” Griffith says. “Lupus particularly affects young women. We’ve made strides with our treatments, but we still have a lot of room to grow. We still have people who fail therapy, we still lose patients at a young age, and we still have patients living with a bad disease that affects their daily life. So that’s why we’re so enthusiastic to participate in these trials.”
→ VIDEO: Larry Moreland, MD, on Rheumatoid Arthritis Treatment Strategies
Engineering T cells and Tregs
Griffith and Moreland’s work focuses on immune T cells, part of the body’s defense system against infection and disease, and a subtype of these cells called Tregs, for regulatory T cells, which normally help to reduce inflammation.
Their various studies involve collecting these cells from a patient’s own body, modifying them in the lab, and then infusing the modified cells back into the patient. The resulting cells are called chimeric antigen receptor T cells (or CAR T cells) and CAR Treg cells.
CAR T-cell therapy has been used for several years in treating various cancers. Cells are given a synthetic receptor that attaches to proteins on the surface of cancer cells, and then they are infused back into the patient so they can attach themselves to cancer cells and kill them.
In the new studies involving autoimmune diseases, the extracted cells are engineered to suppress the immune system’s mistaken attacks on healthy tissue. Often these attacks involve another kind of immune cells, called B cells, that can help to trigger inflammation.
“These modified T cells can target B cells, trying to push them down and hopefully put patient’s autoimmune diseases into remission,” Griffith says.
Overlapping studies
Moreland says that for the last two years, pharmaceutical company Sonoma Biotherapeutics, based near San Francisco, has been backing a phase 1 trial into the use of a CAR Treg therapy called SBT777101 for rheumatoid arthritis patients. Two trial enrollees – one of them a patient of Griffith’s – were treated in late 2024.
“The idea is to increase the number of Treg cells in the synovial tissue to tilt the balance toward more cells that decrease inflammation. We were the first in the country to use this treatment,” Moreland says.
Moreland hopes to find backing from another company to study using CAR T cells to kill B cells more effectively than Rituximab, an existing monoclonal antibody treatment that targets B cells. That research could have implications for treating rheumatoid arthritis, lupus, and myositis, among other autoimmune conditions, he says.
Meanwhile, Griffith says another phase 1 study focuses on CAR T-cell therapy for forms of systemic lupus erythematosus, systemic sclerosis, and inflammatory myositis.
Yet another study will begin this year into using cellular therapy to treat a set of rare autoimmune conditions called antineutrophil cytoplasmic antibody (ANCA) associated vasculitis that cause inflammation of blood vessels. “It’s been treated mainly with Rituximab at two different time points every six months indefinitely, but maybe you can give a patient CAR T cell therapy once every several years, and that could be the only drug they’d need,” Moreland says.
These overlapping studies of using cellular therapy to attack autoimmune diseases “have been a whole divisional effort,” Griffith says. “It’s been with Larry’s guidance that we’re trying to be a leader in cellular therapy.”
It will take years for these various trails to unfold, Moreland says, “so one has to be very patient. The key is to do no harm and go slow.”
Still, “these are exciting times,” says Griffith. “We’re cautiously optimistic.”
→ Learn more about CU Division of Rheumatology research into rheumatic diseases
‘Leaders in the field’
Griffith and Moreland both credit Jonathan Gutman, MD, a professor in the CU Division of Hematology and a noted leader in clinical research in blood cancers, and his colleagues with helping to pioneer the cellular-therapy work in the oncology space that laid the foundation for their research in the rheumatology realm.
“We’re basically following in their footsteps,” Moreland says. “They revolutionized this field of treatments, and we’re relying on their infrastructure and their expertise. They’ve already been there, and we’re just starting.”
“We in the blood cancer world, where cell therapies had their first big successes, are thrilled to see them being extended to other diseases, and we’re excited by their preliminary data in a number of autoimmune diseases,” Gutman says.
“Cell therapies are very complex, and it takes a multidisciplinary village to administer them,” he adds. “The collaborative effort between the cell therapy program and Larry, Melissa, and others in a growing number of disciplines has been great.”
Gutman adds that cellular therapy research on the CU Anschutz Medical Campus “is expanding quite rapidly into new spaces” in addition to rheumatology, including nephrology, neurology, and endocrinology. “We are positioning ourselves well to be leaders in the field going forward,” he says.
Photo at top: Equipment for producing CAR T cells on the CU Anschutz Medical Campus.
