1. Engineered immune cells as therapeutics for autoimmune diseases.
- Author
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Zouali, Moncef
- Subjects
- *
AUTOIMMUNE diseases , *B cells , *SJOGREN'S syndrome , *THERAPEUTICS , *CHIMERIC antigen receptors - Abstract
Immune cells can be equipped with a DNA construct that codes for a chimeric antigen receptor (CAR) specific for pathogenic B lymphocytes, or a chimeric autoantibody receptor (CAAR) that can be specifically recognized by pathogenic B lymphocytes. Engineered immune cells have shown preliminary therapeutic promises in both experimental models and clinical trials of lupus, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, and Sjögren's syndrome, sometimes without any identified systemic toxicity. Engineered immune cells obtained by integrating mRNA, instead of DNA, can also lead to durable remission in autoimmune patients in the absence of generalized immunosuppression. Next-generation platforms are under development to overcome the resistance mechanisms of target cells, optimize their specificity, tune bioengineered immune cell signaling, and improve safety. Current treatment options for autoimmune disease (AID) are essentially immunosuppressive, inhibiting the inflammatory cascade, without curing the disease. Therapeutic monoclonal antibodies (mAbs) that target B cells showed efficacy, emphasizing the importance of B lymphocytes in autoimmune pathogenesis. Treatments that eliminate more potently B cells would open a new therapeutic era for AID. Immune cells can now be bioengineered to express constructs that enable them to specifically eradicate pathogenic B lymphocytes. Engineered immune cells (EICs) have shown therapeutic promise in both experimental models and in clinical trials in AID. Next-generation platforms are under development to optimize their specificity and improve safety. The profound and durable B cell depletion achieved reinforces the view that this biotherapeutic option holds promise for treating AID. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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