Autoimmune disease refers to the disease in which the immune system reacts to the host's own body and causes damage to tissues and organs. At present, the pathogenesis of various autoimmune diseases is still not well understood, but an imbalanced immune tolerance plays a key role in this process.~An ideal therapy to autoimmune disease should eradicate pathogenic autoimmune cells but retain the protective immunity. The chimeric antigen receptor-modified T (CAR-T) cell technology has proven to be highly effective in targeting B cell malignancies, and the treatment-induced B cell and antibody deficiencies have implications for treating autoantibody-related autoimmune diseases. Studies have shown that CAR-T cells targeting B cell surface molecules can kill autoreactive B lymphocytes in pemphigus vulgaris (PV) and systemic lupus erythematosus (SLE) patients. Thus, CAR-T cell technology targeting B cells has potential in treating autoimmune diseases including PV, SLE, autoimmune hemolytic anemia, Sjogren's syndrome etc..~CD19-specific CAR is based on activation of intracellular signalijng domains of T cells by the extracellular single chain variable fragment (scFv) antibody against CD19. The activated CAR-T cells can target and kill B cells. The investigation plans to use genetically modified T cells to express a 4th generation lentiviral anti-CD19 CAR with an inducible caspase 9 self-withdrawal gene (4SCAR) to increase the safety of this specific approach. Besides targeting CD19, specific CARs targeting other B cell surface molecules including BCMA, CD138, and BAFF-R will also be included in the treatment regimen. Based on accumulated experiences, the 4SCAR T cells have shown high safety profile without serious cytokine release syndrome (CRS) or neural toxicities in patients. Through this trial, the safety and long term efficacy of the B cell-specific 4SCAR T cell therapy will be evaluated, providing clinical evidence supporting the application of 4SCAR-T cell technology in the treatment of autoimmune diseases.
The purpose of this study is to assess the feasibility, safety and efficacy of CAR-T cell therapy in patients with autoimmune disease. Another goal of the study is to learn more about the safety and function of the CAR-T cells and their persistency in autoimmune disease patients.