September 21, 2022
Results of a small study published in the prestigious journal Nature Medicine, suggest that a type of immune cell therapy called chimeric antigen receptor (CAR) T cell therapy could become a highly effective therapy for SLE patients who do not respond to current lupus treatments. CD19 CAR T cells are T cells that have been engineered to target and destroy harmful B cells with a unique protein – CD19 – on their surface.
The research that provided the foundation for the current clinical study was funded in part by the Lupus Research Alliance (LRA) 2015 Lupus Innovation Award grant to Dr. Marko Radic from the University of Tennessee Health Science Center. Dr. Radic’s work showed that CD19 CAR T cell therapy effectively depleted the harmful B cells in mice with lupus and induces disease remission. B cells are immune cells responsible for causing many of the symptoms of SLE, as these cells produce autoantibodies that attack the body’s own tissues and organs.
Standard lupus treatments do not entirely relieve disease symptoms for many patients because these treatments do not remove all harmful B cells. Therefore, the German research team led by Dr. Georg Schett, Vice President of Research at the Deutsches Zentrum für Immuntherapie and Professor and Chair at the Department of Internal Medicine at Friedrich Alexander University Erlangen-Nuremberg and Universitätsklinikum in Erlangen, Germany, tested if eliminating all the harmful B cells would push difficult-to-treat SLE into remission. Theoretically, this would then allow lupus patients to stop their other treatments that often have ] harmful side effects.
Dr. Schett and his team worked with a small group of five SLE patients who had not responded to several standard lupus treatments. T cells were purified from the patients’ blood and engineered to express a chimeric antigen receptor (CAR) on their surface—hence, the term CAR T cells—which binds a molecule called CD19 on B cells. The generated CD19+ CAR T cells were then expanded in the lab before being infused back into each patient.
The researchers found that the treatment depleted the CD19 B cells and induced disease remission in all five patients within 3 months. Importantly, drug-free remission was maintained during longer follow-up (currently up to 12 months) and even after the reappearance of B cells. The CD19 CAR T cell treatment was relatively well tolerated, with only mild cytokine-release syndrome.
“These results are very exciting and hold a lot of promise, but they need to be interpreted with caution given the small size of the study and the limited at present long-term follow-up” commented Lupus Research Alliance Chief Scientific Officer Teodora Staeva, PhD. “Further studies in with a larger cohort of lupus patients followed for a longer period of time are needed to determine the safety and efficacy of this novel therapeutic approach in this patient population.”