The American College of Rheumatology publishes a study about a new way to treat a famously slippery autoimmune disease, using CAR-T therapy to successfully put lupus in remission:
Systemic lupus erythematosus (SLE, lupus) is a complex autoimmune disease marked by the production of autoantibodies to nucleic acid DNA and nuclear protein autoantigens and is associated with dysfunctional B cells. It mainly affects women and is more common and severe in people who are Black, Hispanic, or Asian. Lupus can lead to a wide range of systemic problems varying in severity, including skin, kidney, lung, joints, and heart disease and complications during pregnancy.
The disease often requires life-long treatment with immunosuppressive or immunomodulatory drugs, and a considerable number of patients don’t respond to them. One theoretical option for these patients is chimeric antigen receptor (CAR)-T cell therapy, which is successfully used to treat refractory blood cancers by destroying malignant cells.
“We were intrigued by the possibility that a deep B cells depletion exerted by CAR-T cells could lead to permanent eradication of the autoimmune disease,” says Georg Schett, MD, a rheumatologist at the University Hospital Erlangen in Germany.
CAR-T cells are created by removing some of a patient’s white blood cells, including immune system T cells, and genetically altering them in a lab to produce chimeric antigen receptors (CARs). The modifications allow the treated T cells to recognize and destroy antigens on the surface of target pathogenic cells after they are infused back into the patient.
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The study included eight patients, one of whom was an Asian woman. None were Black or Hispanic. Patient T cells were modified using the lentiviral vector MBCART19. Lentiviral vectors are commonly used to deliver genetic material to specific cells in a lab. Between March 2021 and June 2023, each patient received a single dose of one million CD19 CAR-T cells per kilogram of body weight.
The researchers monitored disease activity in the patients for up to two years. Autoantibodies were measured at baseline, three months after CAR-T cell therapy and one to two years post infusion, using enzyme-linked immunosorbent assay (ELISA). Anti-double strand DNA was measured a second time by radioimmunoassay.
The researchers also assessed how patients responded to vaccines against measles, mumps, rubella, varicella zoster virus, Epstein-Barr, tetanus, and pneumococcus.
By June 2023, all eight patients were in remission, had an SLE disease activity (SLEDAI) score of zero and were off all immunosuppressant drugs, including glucocorticoids. Autoantibodies disappeared after CAR-T cell therapy with the exception of a single antibody in one patient and remained negative until the last follow-up, 12 to 24 months after treatment. This was in spite of the re-emergence of naïve B cells a few months after the infusion, which may have played a role in the patients’ robust vaccination response.
“We were surprised by the fact that despite the recurrence of B cells, the disease remained absent,” says Schett. “This outcome is the best one can expect as the presence of B cells permits immune responses against infections and vaccinations, while the disease, including disease-associated autoantibodies, does not come back.”