The autoimmune disease systemic lupus erythematosus, or lupus, is among the leading causes of death in young females. Since 2015, the Yale Lupus Program has conducted clinical trials with the latest and most advanced treatments to better help patients who have difficulty with the disease despite standard therapies, which sometimes lose effectiveness or do not fully control joint pain, fatigue, and skin rash, or prevent internal organ damage.
“We have a keen interest in helping lupus patients with unmet treatment needs, especially those who are not getting better or have frequent relapses,” said Fotios Koumpouras, MD, associate professor of clinical medicine (rheumatology) and director of the Yale Lupus Program.
The main goal of treatment is to reduce the burden of disease and improve function and quality of life, but current medications control the disease by broadly targeting many pathways, which can be associated with serious side effects over the long term. While the disease can be minimized in many cases, drug-free remission rarely occurs.
To provide a better alternative for patients, Koumpouras, together with Department of Internal Medicine residents Nathan Johnson, MD, PhD, Marwin Groener, MD, and the Yale Cancer Center/Smilow Cancer Hospital cellular therapy team, plan to introduce a program that will bring to Yale a recently developed cellular therapy that precisely targets one disease pathway in lupus.
Called chimeric antigen receptor (CAR) T-cell therapy, the technology has been successfully used to treat patients with certain cancers. Koumpouras, Johnson, and Groener are working to apply this novel therapeutic approach to selected lupus patients at Yale.
CAR T-cell therapy has the potential to change the landscape for people with severe lupus, Koumpouras says. “The idea is that you take out a patient’s T cells, engineer them to target autoantibody producing cells that drive inflammation in lupus, and return them to the patient where they can do their work,” he said. “Early results from Europe suggest that an apparent 'reset' of the immune response may occur.”
CAR T-cell therapy is a way of redirecting the body’s own natural immune system through bioengineering, says Johnson. “Using modifications introduced in the lab, we enable the body’s own T cells to effectively seek out and destroy new targets that are the cause of disease,” he said.
In patients with lupus, abnormal B cells create autoantibodies that attack the body’s own organs and tissues, Groener explains. “CAR T cells that target B cells can essentially remove the disease-causing B cells in lupus patients, helping them to achieve a significant improvement in symptoms and potentially long-term remission,” he said.
CAR T-cell therapy is currently FDA-approved to treat some forms of leukemia. Recent small-scale studies have shown that the therapy may induce durable remission in patients with lupus. Groener notes a seminal study in Germany in which remission was induced in five patients for several months with few side effects. The patients continue to be studied to see how long the remission continues and if their symptoms return.
Groener hopes that the development of the CAR T-cell therapy program at Yale will help establish a new and safe method to combat severe lupus. “As the program grows, we hope to make the treatment available to more patients in the health system and possibly apply it to other autoimmune conditions as well,” he said.
Johnson’s goals are to customize specific treatments for individuals and to ensure this next-generation therapy is accessible to all. This kind of patient care, he says, will have a meaningful impact by offering effective treatment to people who have been struggling with difficult-to-treat autoimmune conditions.
Koumpouras points to findings that have spurred a new class of therapeutics for individuals with autoimmune disorders. "Indeed over 20 different cellular therapies originally employed against malignant disorders are now being considered for potential application to rheumatologic diseases," he said.
The new technology will benefit patients who have been referred to the clinic after having tried standard treatments without success, according to Koumpouras, with the goal of providing new options for those who have exhausted all other therapies. In addition, Koumpouras plans to expand the treatment to address other conditions.
”As data continues to emerge to support CAR T in non-malignant disorders, efforts are underway to study individuals with related diseases such as systemic sclerosis, idiopathic inflammatory myopathies, and certain forms of vasculitis," he said.
The Section of Rheumatology, Allergy and Immunology is dedicated to providing care for patients with rheumatic, allergic and immunologic disorders; educating future generations of thought leaders in the field; and conducting research into fundamental questions of autoimmunity and immunology. To learn more, visit Rheumatology, Allergy & Immunology.