CD19 CAR-T cell therapy: a new dawn for autoimmune rheumatic diseases? DOI Creative Commons

Carlos Rangel-Peláez,

Laura Martínez-Gutiérrez,

María Tristán-Manzano

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 17, 2024

Autoimmune rheumatic diseases (ARDs), such as rheumatoid arthritis, systemic lupus erythematosus, and sclerosis, involve dysregulated immune responses causing chronic inflammation tissue damage. Despite advancements in clinical management, many patients do not respond to current treatments, which often show limited efficacy due the persistence of autoreactive B cells. Chimeric antigen receptor (CAR)-T cell therapy, has shown success oncology for malignancies, targets specific antigens involves adoptive transfer genetically engineered T CD19 CAR-T cells, particular, have promise depleting circulating cells achieving remission. This review discusses potential ARDs, highlighting achievements addressing key considerations optimal target populations, CAR construct design, acceptable toxicities, lasting reset, crucial safe effective adoption therapy autoimmune treatments.

Language: Английский

Study on the Mechanism of Jieduquyuziyin prescription Improving the Condition of MRL/lpr Mice by Regulating T Cell Metabolic Reprogramming through the AMPK/mTOR Pathway DOI
Qingmiao Zhu, Yaxue Han, Xiaolong Li

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: 345, P. 119584 - 119584

Published: March 3, 2025

Language: Английский

Citations

0
A new therapeutic pathway in autoimmune diseases: chimeric antigen receptor T cells (CAR-T) targeting specific cell subtypes or antigen-specific B lymphocytes—a brief review DOI Creative Commons

María Fernanda Segovia,

Diana Landoni,

Yohana Defranchi

et al.

Exploration of Immunology, Journal Year: 2025, Volume and Issue: 5

Published: March 4, 2025

In hematological malignancies, autologous immunotherapy with T lymphocytes expressing a chimeric antigen receptor (CAR-T) has been successfully applied. CAR enhances the immuno-cellular effector system directly against cells target antigens. The objective here was to discuss prospects of applying CAR-T and its variants in autoimmune diseases (AIDs) deplete pathogenic autoantibodies by eliminating B plasma cells. play crucial role pathogenesis AID through production autoantibodies, cytokine dysregulation, presentation, regulatory dysfunction. numerous autoreactive clones various autoantigens, such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, myositis, sclerosis, targeting CD19/CD20 B-cell maturation (BCMA) have shown success preclinical clinical studies, representing an innovative option for refractory patients when standard treatments fail. suppression reactive specific antigens using cytolytic carrying autoantibody (CAAR-T) offers promising approach managing AIDs, especially those characterized pemphigus vulgaris, myasthenia gravis, anti-NMDAR encephalitis. CAAR-T allows elimination without compromising general functionality immune system, minimizing common side effects immunosuppressive therapies, including immunobiologicals CAR-T. vitro, preclinical, (phase 1) studies demonstrated efficacy specificity several AIDs; however, extensive trials 3) are required assess their safety applicability. These advances promise enhance precision medicine management offering personalized individual patients.

Language: Английский

Citations

0
Specifically Enhanced Immunosuppression of B Cells with Chimeric Antigen Receptors Modify Mesenchymal Stem Cells DOI
Xiaoyan Zhao,

Jingxi Gao,

Xingyu Zhu

et al.

Stem Cells and Development, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

Recently, cell therapies, including chimeric antigen receptor (CAR) modified T therapy and mesenchymal stem (MSC) therapy, have demonstrated considerable potential for systemic lupus erythematosus (SLE). In this study, a CAR-MSC model was constructed, combining two therapies. The structural domains of the CAR were designed by using anti-CD19 scFv, targeting CD19 on surface B cells intracellular region interferon-gamma receptor, activating JAK-STAT1 signaling pathway. Then we screened identified most effective domain as CAR1, it facilitates MSCs to maintain significantly higher levels JAK2 phosphorylation IDO expression, shown western blot analysis. We also CAR1 could be consistently stably expressed at high in MSCs, transduction did not affect antigenic phenotypic criteria via flow Furthermore, immunofluorescence results showed CAR1-MSCs bind antigen, they activated human resulting expression analysis following co-culture. Besides, when peripheral blood mononuclear (PBMCs) co-cultured with untransduced (UTD-MSCs) vitro, respectively, that percentage CD3+ CD19+ both lower after co-culturing. co-culture group than UTD-MSCs group, whereas similar groups. This suggests increased inhibitory ability had no significant effect inhibit cells. conclusion, successfully constructed enhance cells, facilitating SLE therapy.

Language: Английский

Citations

0
Immunotherapy in Autoimmune Diseases: Current Advances and Future Directions DOI

Mukund M. Pache,

Rutuja R. Pangavhane

Asian Journal of Pharmaceutical Research, Journal Year: 2025, Volume and Issue: unknown, P. 183 - 191

Published: May 5, 2025

Immunotherapy represents a novel approach for managing autoimmune diseases by targeting specific immune cells, cytokines, and checkpoints rather than broadly suppressing the system. Corticosteroids disease-modifying antirheumatic drugs (DMARDs) remain commonly used treatments despite challenges such as lack of specificity significant adverse effects. Immunotherapies, including monoclonal antibodies (mAbs), CAR-T checkpoint inhibitors (ICIs), address underlying causes system dysfunction, offering enhanced effectiveness conditions rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis. Emerging therapies include next-generation CAR-NK gene editing technologies CRISPR, personalized medicine approaches. These innovations allow precise autoreactive cells customization to individual profiles. Although advances are promising, safety issues, high costs, variability in patient response still major hurdles. Key immune-related events infections, while economic barriers significantly limit accessibility. Additionally, therapeutic outcomes highlights need biomarkers predict responses guide selection. AI-based tools could aid stratification drug discovery, enhancing efficacy future. Overall, sustained exploration immunotherapy optimization introduction new concepts utmost importance purpose disease management. Furthermore, these advancements hold potential extend remission duration improve quality life.

Language: Английский

Citations

0
CD19 CAR-T cell therapy: a new dawn for autoimmune rheumatic diseases? DOI Creative Commons

Carlos Rangel-Peláez,

Laura Martínez-Gutiérrez,

María Tristán-Manzano

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 17, 2024

Autoimmune rheumatic diseases (ARDs), such as rheumatoid arthritis, systemic lupus erythematosus, and sclerosis, involve dysregulated immune responses causing chronic inflammation tissue damage. Despite advancements in clinical management, many patients do not respond to current treatments, which often show limited efficacy due the persistence of autoreactive B cells. Chimeric antigen receptor (CAR)-T cell therapy, has shown success oncology for malignancies, targets specific antigens involves adoptive transfer genetically engineered T CD19 CAR-T cells, particular, have promise depleting circulating cells achieving remission. This review discusses potential ARDs, highlighting achievements addressing key considerations optimal target populations, CAR construct design, acceptable toxicities, lasting reset, crucial safe effective adoption therapy autoimmune treatments.

Language: Английский

Citations

1