Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee

Greco, Raffaella; Alexander, Tobias; Del Papa, Nicoletta; Müller, Fabian; Saccardi, Riccardo; Sanchez-Guijo, Fermin; Schett, Georg; Sharrack, Basil; Snowden, John A.; Tarte, Karin; Onida, Francesco; Sánchez-Ortega, Isabel; Burman, Joachim; Castilla Llorente, Cristina; Cervera, Ricard; Ciceri, Fabio; Doria, Andrea; Henes, Jörg; Lindsay, James; Mackensen, Andreas; Muraro, Paolo A.; Ricart, Elena; Rovira, Montserrat; Zuckerman, Tsila; Yakoub-Agha, Ibrahim; Farge, Dominique

doi:10.1016/j.eclinm.2024.102476

eClinicalMedicine

2024

DOI: 10.1016/j.eclinm.2024.102476

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Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee

Raffaella Greco,

Tobias Alexander,

Nicoletta Del Papa

et al.

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Cited by 15 publications

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

Brittain,

Roldan,

Alexander

et al. 2024

Annals of Neurology

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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

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

Brittain,

Roldan,

Alexander

et al. 2024

Annals of Neurology

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The Future of CAR T Therapeutics to Treat Autoimmune Disorders

Pecher,

Hensen,

Lengerke

et al. 2024

Mol Diagn Ther

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The concept of chimeric antigen receptor (CAR) T cell therapy emerged from cancer immunotherapy and has been rapidly adapted and developed for the treatment of autoimmune, especially B-cell-driven, diseases since the first publication of an article featuring a patient with systemic lupus erythematosus in 2021. Phase II studies are about to start, but up to now, only case reports and small series have been published. In contrast to hemato-oncological diseases, where an aggressive response to malignant cells and long-lasting persistence of CAR T cells has been aimed at and observed in many patients, this is not the case with autoimmune diseases but might not be necessary to control disease. Future studies will focus on the optimal target but also on the optimal level of immunogenicity. The latter can be influenced by numerous modulations that affect not only cytokine release but also regulation. In addition, there are potential applications in regulatory cells such as CAR regulatory T cells (Treg). The question of toxicity reduction must also be addressed, as long-term complications such as the potential development of malignant diseases, infections, or cytopenia must be considered even more critically in the area of autoimmune diseases than is the case for patients with oncologic diseases. Alternative antibody-based therapies using the same target (e.g., CD3/CD19 bispecific targeting antibodies) have not been used in these patients and might also be considered in the future. In conclusion, CAR T cell therapy represents a promising therapeutic approach for autoimmune diseases, offering a targeted strategy to modulate immune responses and restore immune tolerance.

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Harnessing the potential of CAR-T cell in lupus treatment: From theory to practice

Alsuliman,

Marjanovic,

Rimar

et al. 2024

Autoimmunity Reviews

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Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee

Cited by 15 publications

References 79 publications

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

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

The Future of CAR T Therapeutics to Treat Autoimmune Disorders

Harnessing the potential of CAR-T cell in lupus treatment: From theory to practice

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