Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus

Jin, Xuexiao; Xu, Qin; Pu, Chengfei; Zhu, Keqing; Lu, Cheng; Jiang, Yu; Xiao, Lanbo; Han, Yongmei; Lu, Linrong

doi:10.1038/s41423-020-0472-1

Cited by 95 publications

(59 citation statements)

References 30 publications

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“…102 Furthermore, CD19-targeted CAR-T cells also have the potential to eliminate B cells and control SLE. 105 Other autoimmune diseases, such as autoimmune pancreatitis (AIP), psoriasis, rheumatoid arthritis, systemic vasculitis and ulcerative colitis, also show different patterns of cytokine elevation and different degrees of fever during disease progression. AIP is associated with increased production of type I IFN and is characterized by elevated IFN-I-dependent IL-33 production, which leads to fibrotic and inflammation responses.…”

Section: Crs In Pathogenic Diseases Crs In Covid-19mentioning

confidence: 99%

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Shao

Zhang

et al. 2021

Sig Transduct Target Ther

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Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening complication, which is clinically characterized by persistent high fever, hyperinflammation, and severe organ dysfunction. However, CRS is a double-edged sword, which may be both helpful in controlling tumors/viruses/infections and harmful to the host. Although a high incidence and high levels of cytokines are features of CRS, the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear. In the present review, we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS. Considering that CRS is the major adverse event in human diseases and intervention therapy, our review delineates the characteristics, kinetics, signaling pathways, and potential mechanisms of CRS, which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

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Section: Crs In Pathogenic Diseases Crs In Covid-19mentioning

confidence: 99%

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Shao

Zhang

et al. 2021

Sig Transduct Target Ther

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“…Breaking the immune tolerance towards autoreactive immune cells induces specific cytotoxic death of these cells, which may downregulate the immune overactivation driving autoimmunity. Indeed, CAR-T cell therapy targeting CD19 has recently been demonstrated to be effective in the prevention and treatment of a murine model of systemic lupus erythematosus [ 89 ].…”

Section: Cell-based Therapiesmentioning

confidence: 99%

Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD

Derdelinckx

Reynders

Wens

et al. 2021

IJMS

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Cell-based therapies are gaining momentum as promising treatments for rare neurological autoimmune diseases, including neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. The development of targeted cell therapies is hampered by the lack of adequate animal models that mirror the human disease. Most cell-based treatments, including HSCT, CAR-T cell, tolerogenic dendritic cell and mesenchymal stem cell treatment have entered early stage clinical trials or have been used as rescue treatment in treatment-refractory cases. The development of antigen-specific cell-based immunotherapies for autoimmune diseases is slowed down by the rarity of the diseases, the lack of surrogate outcomes and biomarkers that are able to predict long-term outcomes and/or therapy effectiveness as well as challenges in the manufacturing of cellular products. These challenges are likely to be overcome by future research.

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“…Combining both antigen-binding and T-cell activating functions into a single receptor, CAR are receptor proteins that have been engineered to give T cells the new ability to target a specific protein. Sustained B cell depletion by CD19/20-targeted CAR T cells is a highly effective treatment for murine lupus erythematosus and human acute B cell lymphoblastic leukemia [ 143 , 144 ]. Following this rationale, a promising phase 1 study tested safety and efficacy of anti-CD19/20 CAR T cells in the treatment of patients with AQP4-IgG seropositive NMOSD but was withdrawn due to insufficient patient recruitment ( NCT03605238 ).…”

Section: Current and Evolving Therapeutic Strategies In Nmosdmentioning

confidence: 99%

B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

Traub¹,

Husseini

Weber

2021

Pharmaceuticals

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The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

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Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus

Cited by 95 publications

References 30 publications

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD

B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

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