CAR-T cell therapy has achieved groundbreaking success in the treatment of hematologic malignancies, showcasing the immense potential of immunotherapy. As our understanding of immune mechanisms deepens, researchers have increasingly turned their attention to autoimmune diseases. Since B cells play a key role in the pathogenesis of many autoimmune disorders, CAR-T therapy—capable of precisely and deeply eliminating pathogenic B cells—has emerged as a novel and promising strategy. In this special feature, we invite Dr. Jinying Jin and Dr. Yajing Zhang to explore the latest progress and clinical applications of CAR-T therapy in the field of autoimmune diseases.

 

Current Landscape of Autoimmune Disease Treatment

 

Under normal circumstances, the immune system defends the body without attacking its own tissues. However, in autoimmune diseases, this recognition breaks down. The immune system mistakenly targets and attacks the body’s own cells—affecting joints, skin, glands, blood vessels, and multiple organ systems—leading to chronic inflammation and tissue damage. Common autoimmune diseases include systemic lupus erythematosus (SLE), Sjögren’s syndrome, systemic sclerosis, dermatomyositis, rheumatoid arthritis (RA), and ANCA-associated vasculitis (AAV). These diseases often involve multi-systemic involvement and the presence of various autoantibodies.

 The pathogenesis is complex, involving genetic, environmental, infectious, and hormonal factors. Most autoimmune diseases are chronic, relapsing, and currently incurable. Thus, clinical treatment aims to relieve symptoms, reduce flares, and maintain patients’ quality of life.

🔹 Mainstream treatments include:

• Glucocorticoids: Powerful anti-inflammatory agents, often first-line during acute flares.
• Immunosuppressants (e.g., cyclophosphamide, methotrexate, leflunomide): Help control abnormal immune activity and reduce recurrence.
• Biologics (e.g., TNF-α inhibitors, IL-6 blockers, anti-CD20 antibodies): Used especially in refractory connective tissue diseases.
• Small-molecule JAK inhibitors: Offer oral, targeted regulation for select inflammatory conditions.

With advancements in research, autoimmune disease treatment is evolving from broad-spectrum immunosuppression to targeted modulation and personalized management, making long-term disease control and a return to normal life increasingly achievable.

 

CAR-T Therapy: From Targeted Clearance to Immune Rebuilding

 

In certain autoimmune diseases, pathogenic B cells are considered the culprits, producing autoantibodies and activating T cells via antigen presentation and cytokine release, driving systemic inflammation and organ damage.

CAR-T therapy involves isolating T cells from a patient, genetically modifying them to express chimeric antigen receptors (CARs) that recognize specific antigens (e.g., CD19 or BCMA), expanding them ex vivo, and reinfusing them into the patient. These engineered cells seek out and eliminate abnormal B cells, disrupting the disease process at its root.

Think of CAR-T as transforming regular soldiers into elite commandos equipped with radar—precisely eliminating the “enemy cells” that fuel inflammation and tissue injury.

 Why CAR-T is superior to traditional B cell-targeted therapies:

• Anti-CD20 monoclonal antibodies like rituximab can suppress B cells short-term but fail to eliminate long-lived plasma cells or cells in tissues, leading to incomplete remission and relapse.
• CAR-T cells targeting CD19 or BCMA can deeply penetrate tissues and eliminate broader B cell subsets, offering a more durable response.
• More importantly, CAR-T therapy facilitates immune reconstruction. After pathogenic B cells are eliminated, the immune system begins producing healthy, naïve B cells—establishing a new, balanced immune homeostasis.

This "clearance + reconstruction" dual action makes CAR-T a potentially curative option in select B cell–mediated autoimmune diseases.

 

 Clinical Advances in CAR-T for Autoimmune Diseases

 

Since 2011, China has been at the forefront of CAR-T research and early clinical translation. Today, China is a global leader in CAR-T manufacturing, mechanistic studies, and new indications.

Chinese teams have pioneered clinical trials in autoimmune diseases, achieving world-class results. Notably, a universal CAR-T study targeting polymyositis and systemic sclerosis was published in Cell and named one of Science’s Top 10 Breakthroughs of 2024—a major milestone that validated CAR-T’s efficacy in autoimmune diseases and broadened its therapeutic scope.

The landmark application of CAR-T in systemic lupus erythematosus (SLE) has opened doors to other B cell–driven autoimmune conditions, including:

• Systemic sclerosis
• Sjögren’s syndrome
• ANCA-associated vasculitis
• Myasthenia gravis
• Autoimmune hepatitis
• Membranous nephropathy
• Polymyositis

Diseases mediated primarily by T cells or non–antibody pathways—such as type 1 diabetes, ulcerative colitis, ankylosing spondylitis, and psoriasis—are currently less suitable for CAR-T therapy.

Most common CAR-T targets in autoimmune trials:

• CD19: Expressed throughout B cell development
• BCMA: Covers plasma cells and long-lived plasma cells

This enables CAR-T to deliver a full-spectrum immune reset, from progenitor to effector B cells.

 

Emerging Platforms: Beyond Autologous CAR-T

 

Beyond traditional autologous CAR-T, new formats are rapidly emerging:

Format	Features
Autologous CAR-T	Patient-derived, high compatibility, stable in vivo expansion
Universal (Allogeneic) CAR-T	Donor-derived, off-the-shelf, ideal for patients unable to provide autologous cells
CAR-NK	Natural killer–based, with better safety and MHC-independence

Based on clinical experience, autologous CAR-T currently offers the most stable efficacy in autoimmune diseases.

 

Patient Selection: Scientific Screening Is Key

 

While CAR-T shows immense promise, not all autoimmune patients are eligible. Careful mechanism-based selection and individualized assessment are essential for safety and efficacy.

Selection considerations:

• Disease must be primarily B cell– or plasma cell–driven
• Patient must be fit for lymphodepletion preconditioning
• Adequate T cell quality for autologous manufacturing; if not, universal CAR-T may be considered
• Effect onset is not immediate: The full "clearance-reconstruction-remission" cycle may take 3–6 months
• Close monitoring is required for autoantibody titers, complement normalization, and B cell reconstitution
• Steroids or immunosuppressants must be tapered gradually post-treatment to avoid rebound

 

Outlook: Toward a New Era in Autoimmune Therapy

 

With deeper scientific understanding and ongoing technological advances, CAR-T therapy is expanding its reach into refractory autoimmune diseases, offering a beacon of hope to patients with limited options.

As more high-quality clinical trials mature, and platforms become more scalable, precise, and accessible, CAR-T is poised to become a mainstream, personalized, and affordable option, ushering in a new era of autoimmune disease treatment.