CAR T cells in autoimmunity: game changer or stepping stone?
Mougiakakos D, Meyer EH, Schett G (2025)
Publication Type: Journal article
Publication year: 2025
Journal
Abstract
The advent of chimeric antigen receptor (CAR) T cells has revolutionized the treatment landscape for hematologic malignancies, and emerging evidence suggests their potential in autoimmune diseases (AIDs). This article evaluates the early successes and future implications of B-cell–targeting CAR T-cell therapy in AIDs. Initial applications, particularly in refractory systemic lupus erythematosus, have demonstrated significant and durable clinical remissions, with accompanying evaluation of the immune system suggesting a so-called “reset” of innate inflammation and adaptive autoimmunity. This has generated widespread interest in expanding this therapeutic approach. CAR T cells offer unique advantages over other treatment modalities, including very deep B-cell depletion and unique therapeutic activity within inflamed tissues and associated lymphoid structures. However, the field must address key concerns, including long-term toxicity, particularly the risk of secondary malignancies, and future accessibility given the higher prevalence of AIDs compared with malignancies. Technological advances in cell therapy, such as next-generation CAR T cells, allogeneic off-the-shelf products, and alternative cell types, such as regulatory CAR T cells, are being explored in AIDs to improve efficacy and safety. In addition, bispecific antibodies are emerging as potential alternatives or complements to CAR T cells, potentially offering comparable efficacy without the need for complex logistics, lymphodepletion, and the risk of insertional mutagenesis. As the field evolves, cellular therapists will play a critical role in the multidisciplinary teams managing these complex cases. The transformative potential of CAR T cells in AIDs is undeniable, but careful consideration of safety, efficacy, and implementation is essential as this novel therapeutic approach moves forward.
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United States (USA) (US)
Germany (DE)How to cite
APA:
Mougiakakos, D., Meyer, E.H., & Schett, G. (2025). CAR T cells in autoimmunity: game changer or stepping stone? Blood. https://doi.org/10.1182/blood.2024025413
MLA:
Mougiakakos, Dimitrios, Everett H. Meyer, and Georg Schett. "CAR T cells in autoimmunity: game changer or stepping stone?" Blood (2025).
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