Expanding the Role of CAR-T Cell Therapy to Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder resulting from autoantibodies produced by B-cell derived plasma cells. Clinical presentation ranges from mild skin rash to multiorgan failure. Regardless of the clinical presentation or severity of the disease, patients with SLE often require life-long treatment. Current treatment recommendations for SLE include hydroxychloroquine, glucocorticoids, immunomodulatory agents, cyclophosphamide, and biologic agents. Despite availability of these agents, the condition of some patients with SLE progressively worsens. With limited treatment options, new and novel therapeutic approaches are needed. Given the active role of B cells in the pathophysiology of SLE, they present an attractive target for therapies evolving in the oncology field. Amongst these, immune effector cell therapies, including chimeric antigen receptor (CAR)-T cell therapy, have proven beneficial in targeting B cells. The eradication of B cells, along with the potential for T cell persistence, has resulted in prolonged remission or stable disease. This review provides an overview of the pathophysiology of SLE; current treatment options, including monoclonal antibodies targeting cluster of differentiation-20 (CD20), CD22, and B cell-activating factor (BAFF); and explores why and how immune effector cell therapies may prove a promising therapeutic option for this patient population, particularly for individuals with refractory disease. Clinical implications from currently approved U.S. Food and Drug Administration (FDA) agents for haematologic malignancies are discussed and provide insight into considerations for applying this therapy to the patient population with SLE in the context of clinical trials.