Basel, Switzerland – Chimeric antigen receptor (CAR) T-cell therapy represents one of the most significant advancements in modern immunotherapy. Originally developed to treat hematologic malignancies, this approach involves genetically modifying a patient’s T cells to express an artificial receptor capable of recognizing specific tumor antigens. Upon re-infusion, these tailored T cells selectively identify and eliminate malignant cells that evade recognition by the traditional immune system.
As CAR T cells continue to demonstrate exceptional clinical success in oncology, particularly in B-cell leukemias and lymphomas, their use is expanding rapidly into new therapeutic territories. One of the most promising new applications is the treatment of systemic autoimmune and neurologic diseases that are refractory to traditional immunomodulatory therapies.
CAR T Cells: Mechanism and Rationale for Use in Autoimmunity
CAR T cells are engineered to express synthetic receptors that combine antigen recognition with T-cell activation domains. This design allows T cells to respond directly to antigen-expressing cells without the need for major histocompatibility complex (MHC) presentation.
In autoimmune and neuroimmune diseases, dysregulated B cells often play a central role in the production of pathogenic antibodies and maintenance of immune dysfunction. The most widely used therapeutic construct in this context is the CD19-directed CAR, targeting CD19-positive B-cell populations including:
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Long-lived plasma cells
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Plasmablasts
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Memory B cells
These cell subsets can persist even after conventional B-cell–depleting therapies—such as rituximab—lifting the need for a more targeted and durable approach such as CAR T-cell therapy.
Clinical Evidence in Refractory Neuroautoimmunity
Over the last few years, published case series and ongoing trials have reported encouraging outcomes in patients with severe neuroautoimmune diseases that have failed multiple immunotherapies. Among the conditions studied are:
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Myasthenia gravis (MG)
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Stiff person syndrome (SPS)
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Neuromyelitis optica spectrum disorders
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Myositis
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Multiple sclerosis
Several individuals with progressive and debilitating MG or SPS, unresponsive to rituximab and other biologics, have exhibited dramatic clinical improvement following CD19 CAR T-cell infusion. In many cases, these benefits have proven durable, supporting the possibility of long-term immune reprogramming rather than temporary disease control.
Notably, some patients with coexisting autoimmune diseases—such as SPS and MG concurrently—have experienced improvements in both conditions after a single treatment course, demonstrating the broad immunomodulatory potential of CD19 CAR T cells.
Beyond B Cells: A Broader Immunologic Impact
Although CAR T cells primarily target B-cell populations, clinical results suggest therapeutic benefit even in diseases where the autoantibodies involved may not be directly pathogenic. This observation supports several possible mechanisms, including:
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Indirect modification of T-cell subsets
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Elimination of antigen-presenting cells driving autoimmune activation
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Resetting of immune memory networks
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Tissue-resident regulatory effects
Moreover, CAR T cells differ fundamentally from standard biologics: they are living therapies. They can migrate into inflamed tissues—including across the blood–brain barrier—expand locally, and persist as memory cells, maintaining long-term surveillance and suppression of autoimmune activity.
Manufacturing and Treatment Process
CAR T-cell therapy involves several highly specialized and regulated steps:
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Leukapheresis – Patient T cells are collected from peripheral blood.
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Genetic Engineering – Viral or non-viral vectors deliver the CAR construct into the T cells.
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Ex vivo Expansion – CAR T cells are multiplied to therapeutic numbers.
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Lymphodepletion Chemotherapy – The patient receives conditioning treatment to enhance CAR T engraftment.
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Re-infusion – CAR T cells are administered intravenously.
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In vivo Expansion and Activity – The engineered cells proliferate, target pathological cells, and exert immune effects.
This multistep process poses challenges including manufacturing complexity, cost, individualized production, and logistical delays. However, advances in automation, universal donor CAR T cells, and in-hospital manufacturing platforms are rapidly accelerating scalability and accessibility.
Safety Profile: Differences Between Cancer and Autoimmune Applications
While CAR T therapy is associated with recognized toxicities in oncology—such as cytokine release syndrome (CRS) and neurotoxicity—their severity tends to be significantly lower when used for autoimmune disorders. This difference is attributed to:
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Lower disease burden compared to cancer
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Reduced activation intensity of infused cells
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Different immune microenvironments
In reported autoimmune cases:
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CRS is generally mild and manageable
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Neurologic toxicities are rare
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Infections remain a risk due to B-cell depletion
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Long-term monitoring is essential
Altogether, the emerging data suggests a favorable risk-benefit profile, especially in patients with life-altering disease unresponsive to all other therapies.
Implications for the Future
The rapid progress of CAR T-cell therapy in neuroautoimmune diseases is reshaping expectations for what immune-based treatments can achieve. Its potential benefits include:
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Durable or potentially curative responses
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Targeting of disease mechanisms unreachable by current agents
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Ability to reset immune function toward tolerance
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Single-treatment models replacing chronic lifelong therapy
If long-term studies confirm current observations, CAR T cells may fundamentally shift treatment paradigms for a broad class of refractory autoimmune and neurologic conditions.
Conclusion
From their origins as precision oncology tools, CAR T-cell therapies are emerging as transformative treatments in systemic and neuroautoimmune diseases. CD19 CAR T cells demonstrate the ability to eliminate pathogenic B-cell populations, penetrate physiologic barriers such as the blood–brain barrier, and exert long-lasting immune modulation.
The impressive early success in conditions such as MG and SPS—including in patients resistant to all established therapies—signals the beginning of a new era in autoimmune medicine. As trials continue and mechanisms are further clarified, CAR T-cell therapy has the potential not only to treat but to reset immune dysregulation, offering hope for durable remission and improved quality of life across the spectrum of neuroautoimmunity.
Contact
Prof. Marinos C. Dalakas
Thomas Jefferson University