The Role of Chimeric Antigen Receptor T‐Cell Therapy in Immune‐Mediated Neurological Diseases

Author:

Brittain Gavin12ORCID,Roldan Elisa34,Alexander Tobias56,Saccardi Riccardo7,Snowden John A.34,Sharrack Basil12,Greco Raffaella8ORCID

Affiliation:

1. Neuroscience Institute University of Sheffield Sheffield UK

2. Department of Neurology and Sheffield NIHR Neuroscience BRC Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK

3. Department of Haematology Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK

4. Division of Clinical Medicine, School of Medicine and Population Health University of Sheffield Sheffield UK

5. Department of Rheumatology and Clinical Immunology—Charité–Universitätsmedizin Berlin Corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and the Berlin Institute of Health (BIH) Berlin Germany

6. Deutsches Rheuma‐Forschungszentrum (DRFZ Berlin)—a Leibniz Institute Autoimmunology Group Berlin Germany

7. Cell Therapy and Transfusion Medicine Unit Careggi University Hospital Florence Italy

8. Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Hospital Vita‐Salute San Raffaele University Milan Italy

Abstract

Despite the use of ‘high efficacy’ disease‐modifying therapies, disease activity and clinical progression of different immune‐mediated neurological diseases continue for some patients, resulting in accumulating disability, deteriorating social and mental health, and high economic cost to patients and society. Although autologous hematopoietic stem cell transplant is an effective treatment modality, it is an intensive chemotherapy‐based therapy with a range of short‐ and long‐term side‐effects. Chimeric antigen receptor T‐cell therapy (CAR‐T) has revolutionized the treatment of B‐cell and other hematological malignancies, conferring long‐term remission for otherwise refractory diseases. However, the toxicity of this treatment, particularly cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome, and the complexity of production necessitate the need for a high level of specialization at treating centers. Early‐phase trials of CAR‐T therapies in immune‐mediated B cell driven conditions, such as systemic lupus erythematosus, neuromyelitis optica spectrum disorder and myasthenia gravis, have shown dramatic clinical response with few adverse events. Based on the common physiopathology, CAR‐T therapy in other immune‐mediated neurological disease, including multiple sclerosis, chronic inflammatory polyradiculopathy, autoimmune encephalitis, and stiff person syndrome, might be an effective option for patients, avoiding the need for long‐term immunosuppressant medications. It may prove to be a more selective immunoablative approach than autologous hematopoietic stem cell transplant, with potentially increased efficacy and lower adverse events. In this review, we present the state of the art and future directions of the use of CAR‐T in such conditions. ANN NEUROL 2024;96:441–452

Publisher

Wiley

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