Can CAR T-cell Therapy Revolutionize the Treatment of Autoimmune Neurological Diseases?

Autoimmune neurological diseases, such as myasthenia gravis, multiple sclerosis, or certain encephalitides, are often difficult to treat with current approaches. These conditions occur when the immune system mistakenly attacks components of the nervous system, causing damage and sometimes severe symptoms. Existing treatments, such as corticosteroids or monoclonal antibodies, can reduce flare-ups but do not always completely eliminate the responsible immune cells. However, a new therapeutic approach is emerging: CAR T-cell therapy, already successfully used against certain blood cancers.

This approach involves genetically modifying the patient’s T lymphocytes so that they specifically target and destroy abnormal B lymphocytes that produce harmful auto-antibodies. Unlike conventional treatments, CAR T cells can penetrate deep into tissues, including the central nervous system, and durably eliminate the cells causing the disease. Recent clinical trials have shown promising results in patients with severe myasthenia gravis, neuromyelitis optica, or anti-NMDA receptor encephalitis, with a significant reduction in symptoms and generally moderate side effects.

The principle relies on the ability of CAR T cells to recognize specific markers on the surface of pathogenic B lymphocytes, such as CD19 or BCMA. Once reinjected, these modified cells trigger a targeted immune response, suppressing abnormal B lymphocytes while preserving part of normal immunity. This precision limits the risks of infection or excessive immunosuppression, often observed with other immunosuppressive treatments.

For example, in patients with refractory myasthenia gravis, a single infusion of anti-CD19 CAR T cells led to a lasting improvement in muscle strength and a decrease in auto-antibodies, without causing major toxicity. In neuromyelitis optica, a disease where antibodies attack the spinal cord and optic nerves, anti-BCMA CAR T cells induced prolonged remission in the majority of treated patients, with overall satisfactory tolerance.

Another advantage is the ability to tailor this therapy based on the target of the auto-antibodies. For diseases where the antigen is located outside the cells, such as in myasthenia gravis or anti-NMDA receptor encephalitis, classical CAR T cells are sufficient. For those involving intracellular antigens, such as stiff-person syndrome, variants called CAAR T cells are under development. These cells directly target B lymphocytes producing specific auto-antibodies, offering an even more precise approach.

The underlying mechanisms also explain why side effects, such as cytokine release syndrome, are less frequent and less severe than in cancer. Indeed, the number of pathogenic B lymphocytes is much lower than that of tumor cells, which reduces the extent of the inflammatory reaction. Available data also suggest that healthy B lymphocytes, located in the bone marrow, are not completely eliminated, allowing the maintenance of protective immunity.

While these results are encouraging, questions remain. The duration of remission, the possibility of relapse, and long-term effects require further study. Additionally, this therapy remains complex and expensive, currently reserved for severe and treatment-resistant forms. Several clinical trials are underway to evaluate its effectiveness in other autoimmune neurological diseases, such as multiple sclerosis or rare encephalitides.

This advancement paves the way for more personalized medicine, where the immune system could be “reset” to definitively halt disease progression. If these results are confirmed, CAR T-cell therapy could become a major option for patients who do not respond to conventional treatments, thus transforming the management of these debilitating conditions.

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DOI: https://doi.org/10.1186/s12974-025-03662-6

Title: CAR T cell therapy in autoantibody-mediated neurological disorders: a promising strategy

Journal: Journal of Neuroinflammation

Publisher: Springer Science and Business Media LLC

Authors: Muzi Wen; Ruoyi Zheng; Hanqing Zhang; Sophia Y. Goldberg; Zhiying Jian; Ye Gao; Ruogu Cheng; Linxin Wen; Yu Zhao; Saad S. Kenderian; Pei Shang