Chimeric antigen receptor cell therapy: A revolutionary approach transforming cancer treatment to autoimmune disease therapy

Abstract

Currently, autoimmune disorders are predominantly managed with broad-spectrum immunosuppressive agents and monoclonal antibodies, which can alleviate disease symptoms but are rarely curative and are frequently associated with significant adverse effects. Autoreactive B cells play a key role in the pathogenesis of many autoimmune diseases; however, B-cell-depleting therapies such as rituximab have shown limited efficacy in certain autoimmune diseases, primarily due to the persistence of autoreactive B cells within lymphoid tissues and sites of inflammation. Consequently, there is an urgent need for more effective and targeted therapies for patients with severe and refractory autoimmune conditions. In this context, recent advancements in genetic engineering have facilitated the application of cell-based therapies, which have transitioned from oncology to treating autoimmune diseases. Therapies utilizing chimeric antigen receptor (CAR) engineered immune cells have emerged as a promising and potentially curative approach. Clinical trials targeting CD19-expressing B cells in B cell-driven autoimmune diseases, such as systemic lupus erythematosus (SLE), have yielded encouraging results, demonstrating durable remissions in otherwise treatment-resistant cases. In addition, novel strategies are being developed to broaden the therapeutic scope of CAR-based therapies in autoimmunity, including chimeric autoantibody receptor (CAAR)-T cells designed to eliminate autoantigen-specific B cells selectively and CAR-engineered regulatory T cells (CAR-Tregs) aimed at achieving antigen-specific immune modulation and restoration of self-tolerance. Despite these advances, several challenges persist, including short and long-term safety concerns, limited in vivo persistence, and the high costs associated with personalized cell manufacturing. Innovations in CAR design, such as logic-gated CARs, inducible suicide switches, and universal CAR constructs, are under active investigation to enhance safety, control, scalability, and clinical accessibility.

Keywords: Autoimmune disease; CAR-NK; CAR-T; CAR-cell therapy; Chimeric antigen receptor (CAR); Immunotherapy.