Immunotherapies such as CAR T-cell therapy were originally developed mainly to fight cancer, but scientists are now investigating whether these personalized treatments, made from a patient's own immune cells, could also help treat or even potentially cure autoimmune diseases like rheumatoid arthritis, a chronic condition where the immune system mistakenly attacks the joints, causing swelling and eventual damage that often requires lifelong medication with significant side effects.
For patients with treatment-refractory rheumatoid arthritis who have exhausted multiple therapies, researchers at Charité - Universitätsmedizin Berlin conducted the world's first clinical trial of its kind, reported in Nature Medicine, using CD19-CAR T-cell therapy to target disease-driving B cells that survive in lymph nodes, bone marrow, or joint tissue; "One reason could be disease-driving B cells - memory cells of the adaptive immune system that may survive in the lymph nodes, bone marrow or joint tissue after an infection, where they produce harmful antibodies directed against the body's own tissues and repeatedly reignite the inflammation," explains Prof. David Simon, who designed the trial.
The therapy involves collecting a patient's T cells, genetically modifying them in the laboratory to express a chimeric antigen receptor (CAR) that acts as a "search sensor" for the CD19 "name tag" found on harmful B cells, and then reinfusing them after preparatory chemotherapy to seek out and eliminate these cells deep within tissues, effectively giving the B-cell system a new start. 
This approach proved highly promising in the first phase of the COMPARE trial, which enrolled six patients with severe disease who had failed up to eight prior treatments; "Disease activity decreased markedly in all six patients. During follow-up of up to one year, three patients were in sustained remission without any medication for rheumatoid arthritis," reports Gerhard Krönke, noting this is "particularly remarkable given that none of the established treatments had previously been able to relieve their symptoms adequately." 
Imaging confirmed that inflammatory foci were no longer detectable months after therapy, and follow-ups showed a sharp drop in autoantibodies while protective antibody memory from vaccinations remained intact, with David Simon adding: "When the B-cell system later recovered, predominantly naïve B cells that had not yet been shaped by the disease returned. 
In contrast, the B cells directed against the body's own tissues that had been present before treatment were no longer detectable in almost all patients, an indication that the treatment may indeed be able to reset the pathological immune memory."  Although one patient experienced a return of disease and others showed varying responses, the safety profile was encouraging; "After the participants received the CD19 CAR T cells, we observed only a temporary, mild-to-moderate cytokine release syndrome (CRS) in all participants, which was readily manageable.