Clinical trials to study new use for CAR T-cell therapy: treating autoimmune diseases
The University of Chicago Medicine has launched a Phase 2 clinical trials to study how CAR T-cell therapy could be used to treat three autoimmune diseases: systemic lupus erythematosus, inflammatory myositis and systemic sclerosis (also known as systemic scleroderma).
Initially used in the treatment of blood cancers, CAR T-cell therapy was first approved by the FDA in 2017 to treat certain types of B-cell lymphoma in adults.
The therapy involves removing a patient’s own T cells and genetically engineering them to express a surface protein called a chimeric antigen receptor (CAR) to target specific cells contributing to disease. Once reintroduced to the body, the supercharged T cells help a patient's immune system attack the disease.
UChicago Medicine experts anticipate a wider potential for the groundbreaking therapy.
“We are starting to expand from the field of oncology to other areas of medicine, such as rheumatology and neurology,” said Satyajit Kosuri, MD, a cellular therapy physician and an Assistant Professor of Medicine at UChicago Medicine.
CAR T-cell therapy, Kosuri said, “is a broad platform that we can adapt and apply to certain patient populations with diseases that have been resistant to historically standard therapies. It may offer a new solution where previously there was none.”
New uses for CAR T-cell therapy
Currently, the cornerstone treatment in autoimmune diseases is glucocorticoids, such as prednisone, which are used in combination with other medications.
Autoimmune diseases can sometimes be controlled with these medications, but they are likely to flare with discontinuation. They require lifelong treatment with these agents, which carry significant risk of side effects.
The interest in using CAR T-cell therapy for autoimmune diseases is “actually fairly recent,” said Iazsmin Bauer Ventura, MD, a rheumatologist and Assistant Professor of Medicine at UChicago Medicine, with the work “mainly coming from publications by our colleagues in Germany.”
Earlier this year, a study published in the New England Journal of Medicine evaluated CAR T-cell therapy treatment administered to 15 patients, each of whom had one of the same three autoimmune diseases being studied in the new UChicago Medicine clinical trials.
This type of immunotherapy, researchers wrote, is a “feasible, safe and efficacious” option for patients with those diseases, “providing rationale for further controlled clinical trials.”
Bauer Ventura is optimistic about the findings. “Most of their patients have achieved no disease activity at all, or very little disease activity off immunosuppression, which is something that is unheard of when we’re talking about severe systemic autoimmune diseases,” she said.
“We don't have any therapies that get any closer to remission off immunosuppressive therapy in the long term when it comes to autoimmune diseases,” Bauer Ventura said, adding that future findings from the new clinical trials could be “revolutionary” for CAR T-cell therapy use.
A way to ‘reset the immune system’
Although CAR T-cell therapy is now generally considered safe, some patients have experienced difficult and serious side effects, such as neurologic toxicities or cytokine release syndrome, a condition where too many cytokines — or proteins that regulate inflammation and immune response — are released and result in a systemic inflammatory response in the body.
In recent years, doctors have gotten a much better grasp on how to manage those side effects. Because of this and the differences between blood cancers and autoimmune diseases, UChicago Medicine researchers are hopeful that patients in their clinical trials won’t experience as many side effects as the original cohorts treated with the therapy for blood cancers.
When it comes to the autoimmune disease trials, physicians will retrieve T cells from patients, which will then be sent to a lab and engineered to express receptors that target diseased cells. Several weeks later, the supercharged cells will be infused into the patient’s body.
“It’s kind of like an attack dog who knows its purpose and target,” Kosuri said.
Healthy immune systems identify and attack harmful cells like viruses, bacteria or bodily cells that are malfunctioning, like cancer cells. But for people with autoimmune disease, Bauer Ventura said, something went awry during the development of their immune systems that causes their bodies to attack healthy cells, causing an inflammatory response.
“We believe one of the main ‘maestros’ in this process are the B cells,” said Bauer Ventura. “By targeting these cells with CAR T-cell therapy, we believe we can kind of reset the immune system and the immune process that caused the autoimmune disease from the start.”
What to know about the clinical trials
The physicians have a detailed screening process to ensure that patients interested in the trials are the right fit. Candidates will meet with both Kosuri and Bauer Ventura’s teams, including nurse practitioners and research coordinators, and undergo various forms of testing to both ensure they’re a good candidate for the trials and to help measure the efficacy of the treatments.
Patients will also receive a mild chemotherapy regimen to prime their body and regular immune system to accept the newly engineered CAR T cells. The doctors said participants should expect to be hospitalized between four to seven days throughout the process.
UChicago Medicine is one of nine sites for the trials, which is sponsored by Cabaletta, a company specializing in creating CAR T cells for rheumatologic diagnoses. Not every site is offering the treatment for all three of the autoimmune diseases. UChicago Medicine’s trials will be open to adults between the ages of 18 to 75 years old, and it will also include a juvenile protocol for patients with dermatomyositis, open to those under 18.