Researchers of a small study recently shared the highly encouraging results of their research that may lead to new therapeutic approaches against lupus. According to Cleveland Clinic, systemic lupus erythematosus (SLE), or simply lupus, is an autoimmune disease that attacks the body's immune system, affecting the skin, joints, bones, kidneys, and heart.
Although there is no cure for lupus and treatments do not work for many patients, the new study showed that the cancer treatment called anti-CD19 chimeric antigen receptor (CAR) T cell therapy may kick the hard-to-treat autoimmune disease into remission.
High magnification micrograph of histomorphologic changes in a lymph node due to systemic lupus erythematosus
Anti-CD19 CAR T Cell Therapy Used Against Lupus
Teodora Staeva, Ph.D., Chief Scientific Officer for the Lupus Research Alliance (LRA), discussed the results of their study to the Rheumatology Network and its significance to lupus patients.
When asked what motivated the team to use CAR-T therapy as a treatment option for patients with severe lupus, Staeva said that their main goal was to target B cells, which have been a great interest in lupus for a very long time because of their role in the pathogenesis of lupus.
She noted that there are existing therapies, such as rituximab, that also target B cells in the molecule CD20. But two trials using it did not yield a successful result, and the team then decided to investigate for the reason. They hypothesize that perhaps the autoreactive B cells are hidden deep within the lymphoid organs and the inflamed tissue, which makes it harder for the antibody to access it.
Additionally, B cells that are detrimental to the disease have only the molecule CD19 instead of CD20. The current therapy, which was tested in preclinical models and published in two papers in New England Journal of Medicine, effectively targets CD19 and gives promising results.
Study author Dr. Georg Schett, the vice president of research and chair of the department of internal medicine at Friedrich-Alexander University Erlangen-Nürnberg in Germany, said that CAR-T therapy is an established therapy against cancer, particularly lymphoma and leukemia.
According to Medical Xpress, CAR-T therapy works by taking the T-cells of the body and training them in a lab to recognize specific cells and then infusing them again into the body. In lupus patients, it targets the molecule CD19.
The five patients in the study achieved remission after three months of receiving CAR-T therapy alone. They showed improved symptoms, such as remission and disappearance of disease-related autoantibodies. The patients did not undergo any additional treatments after that.
Schett said that severe lupus was very sensitive to CAR-T therapy, and patients could go on longstanding drug-free remission. There were mild side effects compared to cancer studies in which patients would experience high fever and chills, trouble breathing, and cytokine release syndrome.
Significance of the Results and Conducting Further Research
Staeva told Rheumatology Network that the five patients who received the therapy achieved remission even after B cells reappeared, but these patients remained disease-free. It was a phenomenal result for lupus and any other disease, given the severe forms of lupus and the very high disease activity when patients participated in the study.
Before receiving CAR-T therapy, the participants were also subjected to existing treatments; but they had been resistant to them. Staeva noted that the findings are quite remarkable in terms of clinical benefits.
Now, researchers plan to conduct further studies to see if the immune system did undergo a deep reset and to test its safety. They cautioned that it was a small study with only five people in the trial, which means there is not enough information on its long-term effects.
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