Study of BCMA/CD70 CAR-T Therapy for Refractory cSLE

Systemic lupus erythematosus (SLE) is a severe autoimmune disease that can lead to extensive damage in multiple organs and systems, potentially leading to disability and even mortality. Children afflicted with SLE are particularly vulnerable to organ damage, notably affecting the kidneys, and tend to have a more severe and protracted course of the disease compared to adults. Currently, the primary treatment for SLE relies on glucocorticoids and immunosuppressants to alleviate symptoms. However, due to the absence of a curative treatment, patients typically need to remain on medication indefinitely. In recent years, biological agents such as belimumab and rituximab have been introduced for the treatment of SLE, but these treatments cannot completely eliminate autoimmune B cells in the bone marrow, leading to unsatisfactory overall outcomes. Furthermore, discontinuing these drugs can lead to disease relapse, and there is still no cure for SLE, leaving patients facing the challenges of lifelong medication and an incurable disease. BCMA (B Cell Maturation Antigen) is a receptor primarily expressed on the surface of mature B lymphocytes and plasma cells, serving as a marker protein for B lymphocyte maturation. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are the main ligands of BCMA. They interact with BCMA to transmit cellular stimulatory signals, activating TRAF-dependent NF-κB and JNK pathways, thereby increasing the proliferation and survival rate of B cells. Importantly, BCMA is highly expressed in long-lived plasma cells,8 which do not express CD19. Therefore, BCMA can compensate for the targeting defect of CD19's insufficient expression in terminally differentiated plasma cells. CD70 is an immune costimulatory molecule for T and B cells, highly expressed on the surface of activated T cells. The CD70/CD27 pathway regulates immunity and tolerance through various mechanisms, including T-cell expansion and survival, costimulation of antigen presentation, germinal center formation, B-cell activation, and antibody production. It plays a crucial role in the differentiation of B cells into plasma cells. Blocking the CD27/CD70 pathway can inhibit the differentiation of memory B cells into plasma cells. Studies have found that CD70 is overexpressed in B cells of SLE patients compared to healthy individuals. The purpose of this study is to assess the safety and efficacy of the BCMA/CD70 CAR-T cells in the treatment of refractory SLE.