Reimagining Autoimmune Care with CAR-Based Cell Therapies

Chimeric antigen receptor (CAR)-based cell therapy, once considered the exclusive domain of oncology, is gaining momentum in autoimmune disease. In a narrative review published in Frontiers in Immunology in July 2025, Jiang and colleagues outline how CAR T-cell and related technologies are being adapted to treat immune-driven disorders such as lupus, multiple sclerosis, and rheumatoid arthritis. While clinical experience remains limited, there’s mechanistic promise, and early case reports point to potential for sustained, treatment-free remission.

Here's a brief breakdown of the review.

Targeting the Immune System, Not Tumors

For context, traditional CAR T-cell therapy modifies a patient's own T cells to recognize and attack a specific target antigen—typically CD19 on malignant B cells. In autoimmunity, where self-reactive B cells contribute to disease, this same logic is being applied with renewed purpose.

Several reports, including high-profile cases in lupus and autoimmune encephalitis, have shown that anti-CD19 CAR T-cell therapy has the potential to eliminate pathogenic B cells and induce lasting clinical remission, even after conventional therapies fail.

The authors explain that CD19 is an attractive target because it’s expressed not only on naïve and memory B cells, but also on plasmablasts and early plasma cells: cell types that evade depletion by agents like rituximab. By inducing deeper B-cell aplasia, CAR T-cell therapy may interrupt the cycle of autoantibody production that drives ongoing tissue damage in diseases such as systemic lupus erythematosus (SLE).

New Frontiers: CAR Tregs, CAR NKs, and More

Beyond the CD19 paradigm, the review highlights newer strategies now moving through preclinical and early-phase development. One is the chimeric autoantibody receptor (CAAR) T-cell, which uses disease-specific antigens such as DSG3 in pemphigus vulgaris to selectively eliminate autoreactive B cells.

Others include CAR-engineered natural killer (NK) cells and CAR regulatory T-cells (Tregs), both of which offer distinct immunologic advantages. CAR NK cells, for example, may carry lower risk of cytokine release syndrome and graft-versus-host disease, while CAR Tregs aim to restore immune tolerance rather than eliminate cells.

CAR-modified mesenchymal stem cells (CAR-MSCs) are also under investigation for their immunomodulatory and regenerative properties. These may be particularly suited for diseases with both inflammatory and fibrotic components, such as systemic sclerosis or inflammatory bowel disease.

A Look at Potential Challenges

Although the science is advancing rapidly, the authors note several barriers to wider adoption. Safety remains a core concern, especially given the potential for long-term immune suppression or off-target effects. The risk-benefit calculus is different in non-lethal chronic conditions than in cancer, and long-term follow-up data remain sparse. Manufacturing complexity and cost are also major limitations, particularly for personalized autologous therapies.

Still, the early success of anti-CD19 CAR T-cells in small cohorts of patients with refractory lupus and other conditions has shifted the field’s expectations. In several cases, patients were able to discontinue all other immunosuppression, with no disease flare for a year or more following a single infusion.

A Reimagined Therapeutic Landscape

The authors of the review conclude that CAR-based cellular therapies could reshape the treatment landscape for autoimmune disease, moving from chronic immunosuppression to a model of immunologic reset. Much like bone marrow transplant once transformed leukemia care, CAR T-cell therapy may represent a durable intervention that restores immune balance with a single course of treatment. The next steps will require carefully designed trials, longer-term safety monitoring, and deeper mechanistic studies to define who benefits most.

Reference:
Jiang M, Zhao J, Yuan J, et al. Research progress on chimeric antigen receptor-based immunotherapy against autoimmune diseases. Hum Vaccin Immunother. 2025;21(1):2538350. doi:10.1080/21645515.2025.2538350