{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:08:39Z","timestamp":1773446919716,"version":"3.50.1"},"reference-count":149,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Autoimmune diseases (AID) comprise a diverse group of disorders driven by aberrant B-cell and T-cell reactivity against self-tissues. In recent years, cell-based therapies utilizing engineered T cells have emerged as a promising therapeutic strategy for AIDs. Notably, chimeric antigen receptor (CAR)-T cells have demonstrated the ability to selectively target and eliminate autoreactive immune populations, including pathogenic B cells and antibody-producing plasma cells. Beyond T-cell modulation, macrophages (M\u03a6s) exhibit remarkable plasticity, differentiating into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to microenvironmental cues. Advances in genetic engineering have enabled the development of CAR-M\u03a6s (CAR-M), which hold potential for adoptive immunotherapy in certain diseases. However, CAR-M therapy remains experimental and requires further clinical validation. This review systematically evaluates the therapeutic potential of CAR-T and CAR-M in AIDs, comparing their respective advantages and limitations to provide a comprehensive foundation for future translational applications.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1658867","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T06:20:15Z","timestamp":1763619615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineered cell therapies for autoimmune diseases: evaluating CAR-T and CAR-M progress and prospects"],"prefix":"10.3389","volume":"16","author":[{"given":"Mingxuan","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiale","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(23)01126-1","article-title":"Car T-cell therapy in autoimmune diseases","volume":"402","author":"Schett","year":"2023","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.24.10024","article-title":"Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity","volume":"86","author":"Gross","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2107725","article-title":"Cd19-targeted car T cells in refractory systemic lupus erythematosus","volume":"385","author":"Mougiakakos","year":"2021","journal-title":"New Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41392-025-02269-w","article-title":"Car-T cell therapy for cancer: current challenges and future directions","volume":"10","author":"Zugasti","year":"2025","journal-title":"Signal transduction targeted Ther"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.744823","article-title":"Advances in universal Car-T cell therapy","volume":"12","author":"Lin","year":"2021","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36688","article-title":"Chimeric antigen receptors that trigger phagocytosis","volume":"7","author":"Morrissey","year":"2018","journal-title":"eLife"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0462-y","article-title":"Human chimeric antigen receptor macrophages for cancer immunotherapy","volume":"38","author":"Klichinsky","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"100050","DOI":"10.59717\/j.xinn-med.2024.100050","article-title":"Crispra engineered elite macrophages enable adoptive cell therapy for rheumatoid arthritis","volume":"2","author":"Huang","year":"2024","journal-title":"Innov Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1298815","article-title":"Concurrent remission of lymphoma and Sj\u00f6gren\u2019s disease following anti-Cd19 chimeric antigen receptor-T cell therapy for diffuse large B-cell lymphoma: A case report","volume":"14","author":"Sheng","year":"2023","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11899-023-00687-7","article-title":"Car-T cell therapy: the efficacy and toxicity balance","volume":"18","author":"Chohan","year":"2023","journal-title":"Curr hematologic Malignancy Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-024-00903-0","article-title":"Current understanding and management of Car T cell-associated toxicities","volume":"21","author":"Brudno","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.omtm.2016.12.006","article-title":"Global manufacturing of Car T cell therapy","volume":"4","author":"Levine","year":"2017","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.06.014","article-title":"Depletion of high-content Cd14(+) cells from apheresis products is critical for successful transduction and expansion of car T cells during large-scale Cgmp manufacturing","volume":"22","author":"Wang","year":"2021","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04390-6","article-title":"Decade-long leukaemia remissions with persistence of Cd4(+) Car T cells","volume":"602","author":"Melenhorst","year":"2022","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01217","article-title":"Next-generation manufacturing protocols enriching T(Scm) Car T cells can overcome disease-specific T cell defects in cancer patients","volume":"11","author":"Arcangeli","year":"2020","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-024-10185-8","article-title":"In vivo manufacture and manipulation of Car-T cells for better druggability","volume":"43","author":"Hou","year":"2024","journal-title":"Cancer metastasis Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20230903","article-title":"Car-T cell manufacturing: major process parameters and next-generation strategies","volume":"221","author":"Ayala Ceja","year":"2024","journal-title":"J Exp Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.54680\/fr23310110112","article-title":"The role of cryopreservation techniques in manufacturing, transport, and storage of Car-T therapy products","volume":"44","author":"Jandova","year":"2023","journal-title":"Cryo Lett"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-68586-6_2","article-title":"Cytotoxic T cell hybridomas: generation and characterization","volume":"100","author":"Eshhar","year":"1982","journal-title":"Curr topics Microbiol Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2015.1046430","article-title":"Trucks: the fourth generation of cars","volume":"15","author":"Chmielewski","year":"2015","journal-title":"Expert Opin Biol Ther"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12910","article-title":"Implications of macrophage polarization in autoimmunity","volume":"154","author":"Funes","year":"2018","journal-title":"Immunology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4478","article-title":"A novel chimeric antigen receptor containing a Jak-Stat signaling domain mediates superior antitumor effects","volume":"24","author":"Kagoya","year":"2018","journal-title":"Nat Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2024.124779","article-title":"Nanoparticle-mediated universal Car-T therapy","volume":"666","author":"Fan","year":"2024","journal-title":"Int J pharmaceutics"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12218","article-title":"Macrophage phenotypes in atherosclerosis","volume":"262","author":"Colin","year":"2014","journal-title":"Immunol Rev"},{"key":"B25","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s40364-023-00537-x","article-title":"The car macrophage cells, a novel generation of chimeric antigen-based approach against solid tumors","volume":"11","author":"Hadiloo","year":"2023","journal-title":"biomark Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.3390\/cells11101652","article-title":"Induced car-macrophages as a novel therapeutic cell type for cancer immune cell therapies","volume":"11","author":"Su","year":"2022","journal-title":"Cells"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/srep22688","article-title":"Influence of cell physiological state on gene delivery to T lymphocytes by chimeric adenovirus Ad5f35","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1186\/s12967-023-04479-8","article-title":"The application of Her2 and Cd47 car-macrophage in ovarian cancer","volume":"21","author":"Chen","year":"2023","journal-title":"J Trans Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0578-3","article-title":"Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix","volume":"121","author":"Zhang","year":"2019","journal-title":"Br J Cancer"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01687-8","article-title":"A second-generation M1-polarized car macrophage with antitumor efficacy","volume":"25","author":"Lei","year":"2024","journal-title":"Nat Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13045-020-00983-2","article-title":"Pluripotent stem cell-derived car-macrophage cells with antigen-dependent anti-cancer cell functions","volume":"13","author":"Zhang","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e2103258","DOI":"10.1002\/adma.202103258","article-title":"Nanocomplex-mediated in vivo programming to chimeric antigen receptor-M1 macrophages for cancer therapy","volume":"33","author":"Kang","year":"2021","journal-title":"Advanced materials (Deerfield Beach Fla)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"102610","DOI":"10.1016\/j.nantod.2024.102610","article-title":"Lipid nanoparticles produce chimeric antigen receptor macrophages (Car-M) in situ for the treatment of solid tumors","volume":"61","author":"Zhou","year":"2025","journal-title":"Nano Today"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-023-03490-8","article-title":"Chimeric antigen receptor macrophages activated through Tlr4 or Ifn-\u0393 Receptors suppress breast cancer growth by targeting Vegfr2","volume":"72","author":"Duan","year":"2023","journal-title":"Cancer immunology immunotherapy: CII"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-025-06538-0","article-title":"Expanding the frontier of car therapy: comparative insights into Car-T, Car-Nk, Car-M, and Car-Dc approaches","volume":"104","author":"Zhang","year":"2025","journal-title":"Ann Hematol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02017-5","article-title":"Anti-Cd19 Car T cell therapy for refractory systemic lupus erythematosus","volume":"28","author":"Mackensen","year":"2022","journal-title":"Nat Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.07.013","article-title":"Function of novel anti-Cd19 chimeric antigen receptors with human variable regions is affected by hinge and transmembrane domains","volume":"25","author":"Alabanza","year":"2017","journal-title":"Mol Ther"},{"key":"B38","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.jtct.2024.03.023","article-title":"Fully human anti-Cd19 Car T cells derived from systemic lupus erythematosus patients exhibit cytotoxicity with reduced inflammatory cytokine production","volume":"30","author":"Dingfelder","year":"2024","journal-title":"Transplant Cell Ther"},{"key":"B39","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s41232-018-0078-5","article-title":"Transcriptome analysis of peripheral blood from patients with rheumatoid arthritis: A systematic review","volume":"38","author":"Sumitomo","year":"2018","journal-title":"Inflammation regeneration"},{"key":"B40","doi-asserted-by":"publisher","first-page":"9833","DOI":"10.3390\/ijms23179833","article-title":"Role of citrullinated collagen in autoimmune arthritis","volume":"23","author":"Myers","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"16","DOI":"10.4049\/jimmunol.2100643","article-title":"Cd8(+) T cells expressing an Hla-Dr1 chimeric antigen receptor target autoimmune Cd4(+) T cells in an antigen-specific manner and inhibit the development of autoimmune arthritis","volume":"208","author":"Whittington","year":"2022","journal-title":"J Immunol (Baltimore Md: 1950)"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3868","DOI":"10.3390\/polym13223868","article-title":"A review of the effects of collagen treatment in clinical studies","volume":"13","author":"Wang","year":"2021","journal-title":"Polymers"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-225237","article-title":"Shift in perspective: autoimmunity protecting against rheumatoid arthritis","volume":"83","author":"He","year":"2024","journal-title":"Ann rheumatic Dis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217844","article-title":"In vitro elimination of autoreactive B cells from rheumatoid arthritis patients by universal chimeric antigen receptor T cells","volume":"80","author":"Zhang","year":"2021","journal-title":"Ann rheumatic Dis"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.568741","article-title":"Construction of cii-specific Car-T to explore the cytokine cascades between cartilage-reactive T cells and chondrocytes","volume":"11","author":"Liu","year":"2020","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0939-8","article-title":"Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis","volume":"26","author":"Alivernini","year":"2020","journal-title":"Nat Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120390","article-title":"Targeted silver nanoparticles for rheumatoid arthritis therapy via macrophage apoptosis and re-polarization","volume":"264","author":"Yang","year":"2021","journal-title":"Biomaterials"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.867260","article-title":"The role of M1\/M2 macrophage polarization in rheumatoid arthritis synovitis","volume":"13","author":"Cutolo","year":"2022","journal-title":"Front Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0472-1","article-title":"Therapeutic efficacy of anti-Cd19 Car-T cells in a mouse model of systemic lupus erythematosus","volume":"18","author":"Jin","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107487","article-title":"Glucose oxidation-dependent survival of activated B cells provides a putative novel therapeutic target for lupus treatment","volume":"26","author":"Wilson","year":"2023","journal-title":"iScience"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2025.100749","article-title":"Allogeneic Cd19-targeted Car-T therapy in refractory systemic lupus erythematosus achieved durable remission","volume":"6","author":"Wang","year":"2025","journal-title":"Med (New York NY)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jtct.2022.10.004","article-title":"Successful generation of Cd19 chimeric antigen receptor T cells from patients with advanced systemic lupus erythematosus","volume":"29","author":"Kretschmann","year":"2023","journal-title":"Transplant Cell Ther"},{"key":"B53","article-title":"An Open-label, Multi-center, Phase 1\/2 Study to Assess Safety, Efficacy and Cellular Kinetics of YTB323, a Rapid Manufacturing CAR-T Cell Therapy Targeting CD19 on B Cells, for Severe Refractory Systemic Lupus Erythematosus: Preliminary Results","volume":"75","author":"Cort\u00e9s","year":"2023","journal-title":"Arthritis Rheumatola"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1172\/jci129018","article-title":"E4bp4-mediated inhibition of T follicular helper cell differentiation is compromised in autoimmune diseases","volume":"130","author":"Wang","year":"2020","journal-title":"J Clin Invest"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/art.41532","article-title":"Type I interferon-activated Stat4 regulation of follicular helper T cell-dependent cytokine and immunoglobulin production in lupus","volume":"73","author":"Dong","year":"2021","journal-title":"Arthritis Rheumatol (Hoboken NJ)"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1177\/0961203314567750","article-title":"Circulating Cxcr5+Cd4+Helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production","volume":"24","author":"Zhang","year":"2015","journal-title":"Lupus"},{"key":"B57","first-page":"10","article-title":"One year in review 2020: comorbidities, diagnosis and treatment of primary Sj\u00f6gren\u2019s syndrome","author":"Manfr\u00e8","year":"2020","journal-title":"Clin Exp Rheumatol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2015.03.008","article-title":"Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases","volume":"14","author":"Ramos-Casals","year":"2015","journal-title":"Autoimmun Rev"},{"key":"B59","doi-asserted-by":"publisher","first-page":"5","DOI":"10.2174\/1573397112666160714164149","article-title":"Update on pathogenesis of Sjogren\u2019s syndrome","volume":"13","author":"Sandhya","year":"2017","journal-title":"Curr Rheumatol Rev"},{"key":"B60","doi-asserted-by":"publisher","first-page":"9172","DOI":"10.3390\/ijms21239172","article-title":"Innate immunity and biological therapies for the treatment of Sj\u00f6gren\u2019s syndrome","volume":"21","author":"Srivastava","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B61","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/s1474-4422(21)00463-4","article-title":"Advances and ongoing research in the treatment of autoimmune neuromuscular junction disorders","volume":"21","author":"Verschuuren","year":"2022","journal-title":"Lancet Neurol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12367-4","article-title":"Bispecific Bcma\/Cd19 targeted Car-T cell therapy forces sustained disappearance of symptoms and anti-acetylcholine receptor antibodies in refractory myasthenia gravis: A case report","volume":"271","author":"Zhang","year":"2024","journal-title":"J Neurol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1016\/j.neuron.2024.04.014","article-title":"Treatment of concomitant myasthenia gravis and Lambert-Eaton myasthenic syndrome with autologous Cd19-targeted Car T cells","volume":"112","author":"Motte","year":"2024","journal-title":"Neuron"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(23)00194-1","article-title":"Safety and clinical activity of autologous Rna chimeric antigen receptor T-cell therapy in myasthenia gravis (Mg-001): A prospective, multicentre, open-label, non-randomised phase 1b\/2a study","volume":"22","author":"Granit","year":"2023","journal-title":"Lancet Neurol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-024-00043-z","article-title":"B cell lineage reconstitution underlies Car-T cell therapeutic efficacy in patients with refractory myasthenia gravis","volume":"16","author":"Tian","year":"2024","journal-title":"EMBO Mol Med"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2315990121","article-title":"Single-cell analysis of refractory anti-Srp necrotizing myopathy treated with anti-Bcma Car-T cell therapy","volume":"121","author":"Qin","year":"2024","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.8753","article-title":"Cd19-targeting Car T cells for myositis and interstitial lung disease associated with antisynthetase syndrome","volume":"329","author":"Pecher","year":"2023","journal-title":"JAMA"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneuroim.2018.02.015","article-title":"The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis","volume":"318","author":"Chu","year":"2018","journal-title":"J neuroimmunology"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abo0777","article-title":"Antigen-specific depletion of Cd4(+) T cells by Car T cells reveals distinct roles of higher- and lower-affinity Tcrs during autoimmunity","volume":"7","author":"Yi","year":"2022","journal-title":"Sci Immunol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1186\/s12974-024-03262-w","article-title":"Mog-specific Car Tregs: A novel approach to treat multiple sclerosis","volume":"21","author":"Frikeche","year":"2024","journal-title":"J Neuroinflamm"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000200080","article-title":"Car-T cell-mediated B-cell depletion in central nervous system autoimmunity","volume":"10","author":"Gupta","year":"2023","journal-title":"Neurology(R) neuroimmunology Neuroinflamm"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1235222","article-title":"Car-T cells and Car-Tregs targeting conventional type-1 dendritic cell suppress experimental autoimmune encephalomyelitis","volume":"14","author":"Moorman","year":"2023","journal-title":"Front Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adj9730","article-title":"Single-cell analysis of anti-Bcma Car T cell therapy in patients with central nervous system autoimmunity","volume":"9","author":"Qin","year":"2024","journal-title":"Sci Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41392-022-01278-3","article-title":"Anti-Bcma Car T-cell therapy Ct103a in relapsed or refractory Aqp4-Igg seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results","volume":"8","author":"Qin","year":"2023","journal-title":"Signal transduction targeted Ther"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1377322","article-title":"Autoimmune Cd8+ T cells in type 1 diabetes: from single-cell Rna sequencing to T-cell receptor redirection","volume":"15","author":"Yang","year":"2024","journal-title":"Front Endocrinol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.08.004","article-title":"Chimeric antigen receptor (Car) T cells targeting a pathogenic Mhc class ii: peptide complex modulate the progression of autoimmune diabetes","volume":"96","author":"Zhang","year":"2019","journal-title":"J Autoimmun"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2020.104224","article-title":"Towards antigen-specific Tregs for type 1 diabetes: construction and functional assessment of pancreatic endocrine marker, Hpi2-based chimeric antigen receptor","volume":"358","author":"Radichev","year":"2020","journal-title":"Cell Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"315ra189","DOI":"10.1126\/scitranslmed.aad4134","article-title":"Type 1 diabetes immunotherapy using polyclonal regulatory T cells","volume":"7","author":"Bluestone","year":"2015","journal-title":"Sci Trans Med"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112724","article-title":"Regulatory T cell-based therapy in type 1 diabetes: latest breakthroughs and evidence","volume":"140","author":"Huang","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110873","article-title":"Tshr-based chimeric antigen receptor T cell specifically deplete auto-reactive B lymphocytes for treatment of autoimmune thyroid disease","volume":"124","author":"Duan","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1562662","article-title":"Chimeric autoantibody receptor T cells specifically eliminate Graves\u2019 Disease autoreactive B cells","volume":"16","author":"Cheever","year":"2025","journal-title":"Front Immunol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"115644","DOI":"10.1016\/j.bios.2023.115644","article-title":"Current progress, strategy, and prospects of Pd-1\/Pdl-1 immune checkpoint biosensing platforms for cancer diagnostics, therapy monitoring, and drug screening","volume":"240","author":"Ratajczak","year":"2023"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-18-0367","article-title":"Fundamental mechanisms of immune checkpoint blockade therapy","volume":"8","author":"Wei","year":"2018","journal-title":"Cancer Discov"},{"key":"B84","doi-asserted-by":"publisher","first-page":"109625","DOI":"10.1016\/j.biopha.2019.109625","article-title":"Pd-1 disrupted Car-T cells in the treatment of solid tumors: promises and challenges","volume":"121","author":"McGowan","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"B85","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1038\/s41467-024-46654-5","article-title":"Targeting pathogenic Cd8(+) tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis","volume":"15","author":"Zhu","year":"2024","journal-title":"Nat Commun"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.20061","article-title":"Cd19 chimeric antigen receptor-T cell therapy in murine immune thrombocytopenia","volume":"206","author":"Han","year":"2025","journal-title":"Br J haematology"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.124.325212","article-title":"Car-macrophage therapy alleviates myocardial ischemia-reperfusion injury","volume":"135","author":"Wang","year":"2024","journal-title":"Circ Res"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.01.034","article-title":"Chimeric antigen receptor-modified macrophages ameliorate liver fibrosis in preclinical models","volume":"80","author":"Dai","year":"2024","journal-title":"J Hepatol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116604","article-title":"Targeting fibroblast activation protein with chimeric antigen receptor macrophages","volume":"230","author":"Mao","year":"2024","journal-title":"Biochem Pharmacol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113888","article-title":"In vivo Fap-Car macrophages enhance chemotherapy and immunotherapy against pancreatic cancer by removing the fibrosis barrier","volume":"384","author":"Wang","year":"2025","journal-title":"J Controlled release: Off J Controlled Release Soc"},{"key":"B91","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/s0140-6736(21)00733-9","article-title":"Low back pain","volume":"398","author":"Knezevic","year":"2021","journal-title":"Lancet (London England)"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102079","article-title":"Microneedle delivery of Car-M-like engineered macrophages alleviates intervertebral disc degeneration through enhanced efferocytosis capacity","volume":"6","author":"Zhou","year":"2025","journal-title":"Cell Rep Med"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.07.005","article-title":"Frontiers in Car-T cell therapy for autoimmune diseases","volume":"45","author":"Li","year":"2024","journal-title":"Trends Pharmacol Sci"},{"key":"B94","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1056\/NEJMoa2308917","article-title":"Cd19 Car T-cell therapy in autoimmune disease \u2014 a case series with follow-up","volume":"390","author":"M\u00fcller","year":"2024","journal-title":"N Engl J Med"},{"key":"B95","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s00296-024-05772-5","article-title":"Safety and efficacy of Car-T cell therapy in patients with autoimmune diseases: A systematic review","volume":"45","author":"Kattamuri","year":"2025","journal-title":"Rheumatol Int"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1126421","article-title":"B cell depletion therapies in autoimmune diseases: monoclonal antibodies or chimeric antigen receptor-based therapy","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.12.025","article-title":"Anti-Cd20-mediated B-cell depletion in autoimmune diseases: successes, failures and future perspectives","volume":"97","author":"Crickx","year":"2020","journal-title":"Kidney Int"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1002\/art.42652","article-title":"Obexelimab in systemic lupus erythematosus with exploration of response based on gene pathway co-expression patterns: A double-blind, randomized, placebo-controlled, phase 2 trial","volume":"75","author":"Merrill","year":"2023","journal-title":"Arthritis Rheumatol (Hoboken NJ)"},{"key":"B99","doi-asserted-by":"publisher","first-page":"e180012","DOI":"10.1172\/jci180012","article-title":"Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging Car T cell therapies in autoimmunity","volume":"134","author":"Bodansky","year":"2024","journal-title":"J Clin Invest"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1186\/2162-3619-1-36","article-title":"Cd19: A biomarker for B cell development, lymphoma diagnosis and therapy","volume":"1","author":"Wang","year":"2012","journal-title":"Exp Hematol Oncol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031330","article-title":"Bcma is essential for the survival of long-lived bone marrow plasma cells","volume":"199","author":"O\u2019Connor","year":"2004","journal-title":"J Exp Med"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03718-3","article-title":"Bcma-Car T-cells in a patient with relapsing idiopathic inflammatory myositis after Cd19-Car T-cells","volume":"31","author":"M\u00fcller","year":"2025","journal-title":"Nat Med"},{"key":"B103","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12943-023-01735-9","article-title":"Adoptive cellular immunotherapy for solid neoplasms beyond Car-T","volume":"22","author":"Liu","year":"2023","journal-title":"Mol Cancer"},{"key":"B104","doi-asserted-by":"publisher","first-page":"3692","DOI":"10.3390\/cells11223692","article-title":"Car-macrophages and Car-T cells synergistically kill tumor cells in vitro","volume":"11","author":"Liu","year":"2022","journal-title":"Cells"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.011134","article-title":"Glycoengineering of chimeric antigen receptor (Car) T-cells to enforce E-selectin binding","volume":"294","author":"Mondal","year":"2019","journal-title":"J Biol Chem"},{"key":"B106","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s13045-024-01635-5","article-title":"A clinical study of autologous chimeric antigen receptor macrophage targeting mesothelin shows safety in ovarian cancer therapy","volume":"17","author":"Li","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121558","article-title":"Interaction of tumor-associated microglia\/macrophages and cancer stem cells in glioma","volume":"320","author":"Zhu","year":"2023","journal-title":"Life Sci"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103873","article-title":"Car-macrophage: an extensive immune enhancer to fight cancer","volume":"76","author":"Wang","year":"2022","journal-title":"EBioMedicine"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-020-0956-8","article-title":"Value and affordability of Car T-cell therapy in the United States","volume":"55","author":"Fiorenza","year":"2020","journal-title":"Bone marrow Transplant"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.9b00476","article-title":"A chemical switch system to modulate chimeric antigen receptor T cell activity through proteolysis-targeting chimaera technology","volume":"9","author":"Lee","year":"2020","journal-title":"ACS synthetic Biol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202416066","article-title":"Nanoneedle-based electroporation for efficient manufacturing of human primary chimeric antigen receptor regulatory T-cells","volume":"12","author":"Sun","year":"2025","journal-title":"Advanced Sci (Weinheim Baden-Wurttemberg Germany)"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1024362","article-title":"Impact of cryopreservation on Car T production and clinical response","volume":"12","author":"Brezinger-Dayan","year":"2022","journal-title":"Front Oncol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0106-0","article-title":"Clinical use of lentiviral vectors","volume":"32","author":"Milone","year":"2018","journal-title":"Leukemia"},{"key":"B114","doi-asserted-by":"publisher","first-page":"7166","DOI":"10.1038\/s41467-025-62506-2","article-title":"Lung metastasis and recurrence is mitigated by car macrophages, in-situ-generated from Mrna delivered by small extracellular vesicles","volume":"16","author":"Xiao","year":"2025","journal-title":"Nat Commun"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202308377","article-title":"Enhancing car macrophage efferocytosis via surface engineered lipid nanoparticles targeting Lxr signaling","volume":"36","author":"Chuang","year":"2024","journal-title":"Advanced materials (Deerfield Beach Fla)"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01220-3","article-title":"Silencing of Sirp\u03b1 Enhances the antitumor efficacy of Car-M in solid tumors","volume":"21","author":"Zhang","year":"2024","journal-title":"Cell Mol Immunol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-025-01387-8","article-title":"Targeting inflammation with chimeric antigen receptor macrophages using a signal switch","volume":"9","author":"Cao","year":"2025","journal-title":"Nat Biomed Eng"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.Cir-17-0405","article-title":"Reducing ex vivo culture improves the antileukemic activity of chimeric antigen receptor (Car) T cells","volume":"6","author":"Ghassemi","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2024.09.008","article-title":"Successful generation of fully human, second generation, anti-Cd19 Car T cells for clinical use in patients with diverse autoimmune disorders","volume":"27","author":"Mougiakakos","year":"2025","journal-title":"Cytotherapy"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023020023","article-title":"Allogeneic, donor-derived, second-generation, Cd19-directed Car-T cells for the treatment of pediatric relapsed\/refractory Bcp-all","volume":"142","author":"Del Bufalo","year":"2023","journal-title":"Blood"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023020814","article-title":"Allo or auto Car-T cells for refractory Bcp-all","volume":"142","author":"Bader","year":"2023","journal-title":"Blood"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-485623","article-title":"Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy","volume":"121","author":"Teachey","year":"2013","journal-title":"Blood"},{"key":"B123","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/s13046-021-02148-6","article-title":"Mechanisms of cytokine release syndrome and neurotoxicity of Car T-cell therapy and associated prevention and management strategies","volume":"40","author":"Xiao","year":"2021","journal-title":"J Exp Clin Cancer research: CR"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)30363-4","article-title":"Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-act-early): A multicentre, randomised, double-blind, double-dummy, strategy trial","volume":"388","author":"Bijlsma","year":"2016","journal-title":"Lancet (London England)"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0028","article-title":"Fda approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome","volume":"23","author":"Le","year":"2018","journal-title":"oncologist"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008865","article-title":"Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma","volume":"137","author":"Strati","year":"2021","journal-title":"Blood"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001466","article-title":"Blockade of aim2 inflammasome or A1-ar ameliorates Il-1\u03b2 Release and macrophage-mediated immunosuppression induced by Car-T treatment","volume":"9","author":"Liu","year":"2021","journal-title":"J immunotherapy Cancer"},{"key":"B128","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1007\/s10103-024-04146-4","article-title":"The efficacy of high-intensity laser therapy in wound healing: A narrative review","volume":"39","author":"Yoon","year":"2024","journal-title":"Lasers Med Sci"},{"key":"B129","doi-asserted-by":"publisher","first-page":"4890","DOI":"10.1016\/j.cell.2024.06.027","article-title":"Allogeneic Cd19-targeted Car-T therapy in patients with severe myositis and systemic sclerosis","volume":"187","author":"Wang","year":"2024","journal-title":"Cell"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-20-3863","article-title":"Crispr\/Cas9-engineered universal Cd19\/Cd22 dual-targeted Car-T cell therapy for relapsed\/refractory B-cell acute lymphoblastic leukemia","volume":"27","author":"Hu","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1545270","article-title":"Synnotch Car-T cell, when synthetic biology and immunology meet again","volume":"16","author":"Shirzadian","year":"2025","journal-title":"Front Immunol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.09.019","article-title":"Synergistic integration of Mrna-Lnp with car-engineered immune cells: pioneering progress in immunotherapy","volume":"32","author":"Chen","year":"2024","journal-title":"Mol Ther"},{"key":"B133","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s40164-025-00654-3","article-title":"Addressing graft-versus-host disease in allogeneic cell-based immunotherapy for cancer","volume":"14","author":"Lyu","year":"2025","journal-title":"Exp Hematol Oncol"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.10.020","article-title":"Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling","volume":"38","author":"Sena","year":"2013","journal-title":"Immunity"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0725-2","article-title":"Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen","volume":"21","author":"Vardhana","year":"2020","journal-title":"Nat Immunol"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.78.20.11246-11257.2004","article-title":"Antioxidant treatment reduces expansion and contraction of antigen-specific Cd8+ T cells during primary but not secondary viral infection","volume":"78","author":"Laniewski","year":"2004","journal-title":"J Virol"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4275","article-title":"Targeting mitochondrial dysfunction can restore antiviral activity of exhausted Hbv-specific Cd8 T cells in chronic hepatitis B","volume":"23","author":"Fisicaro","year":"2017","journal-title":"Nat Med"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2024.156758","article-title":"Optimizing Car-T cell culture: differential effects of Il-2, Il-12, and Il-21 on Car-T cells","volume":"184","author":"Zhang","year":"2024","journal-title":"Cytokine"},{"key":"B139","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12943-023-01723-z","article-title":"Car-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances","volume":"22","author":"Maalej","year":"2023","journal-title":"Mol Cancer"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13320","article-title":"Monocytes, macrophages, dendritic cells and neutrophils: an update on lifespan kinetics in health and disease","volume":"163","author":"Patel","year":"2021","journal-title":"Immunology"},{"key":"B141","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s40164-024-00549-9","article-title":"The next frontier in immunotherapy: potential and challenges of car-macrophages","volume":"13","author":"Li","year":"2024","journal-title":"Exp Hematol Oncol"},{"key":"B142","doi-asserted-by":"publisher","first-page":"700","DOI":"10.3390\/biom11050700","article-title":"Immunology of acute and chronic wound healing","volume":"11","author":"Raziyeva","year":"2021","journal-title":"Biomolecules"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2015.0635","article-title":"Challenges in the treatment of chronic wounds","volume":"4","author":"Frykberg","year":"2015","journal-title":"Adv Wound Care"},{"key":"B144","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1007\/s12015-024-10806-3","article-title":"Therapeutic properties of M2 macrophages in chronic wounds: an innovative area of biomaterial-assisted M2 macrophage targeted therapy","volume":"21","author":"Nazari","year":"2025","journal-title":"Stem Cell Rev Rep"},{"key":"B145","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1007\/s11033-024-10088-5","article-title":"Mir-146a-5p-enriched exosomes inhibit M1 macrophage activation and inflammatory response by targeting Cd80","volume":"51","author":"Zhang","year":"2024","journal-title":"Mol Biol Rep"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.06.017","article-title":"Ror\u03b1 Induces Klf4-mediated M2 polarization in the liver macrophages that protect against nonalcoholic steatohepatitis","volume":"20","author":"Han","year":"2017","journal-title":"Cell Rep"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202108525","article-title":"Photoresponsive vaccine-like car-M system with high-efficiency central immune regulation for inflammation-related depression","volume":"34","author":"Liu","year":"2022","journal-title":"Advanced materials (Deerfield Beach Fla)"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/8821610","article-title":"Regulatory mechanism of M1\/M2 macrophage polarization in the development of autoimmune diseases","volume":"2023","author":"Peng","year":"2023","journal-title":"Mediators Inflammation"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1022-2","article-title":"Targeting Tyro3, Axl and Mertk (Tam receptors): implications for macrophages in the tumor microenvironment","volume":"18","author":"Myers","year":"2019","journal-title":"Mol Cancer"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1658867\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T06:20:15Z","timestamp":1763619615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1658867\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":149,"alternative-id":["10.3389\/fimmu.2025.1658867"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1658867","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]},"article-number":"1658867"}}