Novel cellular engineered therapeutics targeting autoreactive B cells in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder affecting millions of patients worldwide; it is characterized by dysregulated B cells attacking healthy tissues. Current treatments are limited in their efficacy and often come with significant side effects, such as increased infection risk. Recent advancements in targeted therapies offer potential new treatment avenues by addressing specific immune pathways involved in SLE. This review explores the immunology of SLE, the role of immune dysregulation in its pathogenesis, and the current treatment landscape, highlighting the emerging potential of novel therapies such as CAR T-cell therapies, anifrolumab, belimumab, and bispecific T-cell activators. Although promising, these new therapies present challenges, including long-term efficacy and safety concerns, underscoring the need for further research to optimize treatment strategies and improve patient outcomes. A CAR T-cell therapy is proposed which uses genetically engineered CAR expressing allogeneic T cells; partly derived from cryopreserved leukapheresis products of patients with SLE; that are programmed to recognize and bind to surface markers CD11c, CD86 and CD40L, which are overexpressed in SLE patients, and uniquely found on autoreactive B cells. By focusing on these specific markers, the proposed therapy aims to reduce disease progression while avoiding the depletion of non-autoreactive B cells, thus minimizing adverse effects.