{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:10:29Z","timestamp":1790302229398,"version":"4.1.0"},"reference-count":137,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"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>The application of Chimeric Antigen Receptor T-cell (CAR-T), CAR-engineered regulatory T cell (CAR-Treg) and hematopoietic stem cell (HSC) therapies has grown in recent years, driven by an increasing demand for robust, antigen-specific T lymphocytes for the treatment of both cancer and autoimmune diseases. This review begins by examining existing cell-based therapies, its biological principles and mechanisms, that have helped achieve notable success in treating cancer. The review then discusses the applicability of these approaches to autoimmune diseases such as progressive and relapsing Multiple Sclerosis (MS) and Type 1 Diabetes Mellitus (T1D). We discuss the substantial promise of CAR-T and CAR-Treg therapies and highlight the role of HSCs, while detailing their mechanism of action, manufacturing processes and ongoing clinical trials. We also examine key challenges such as on and off-target effects, dependence on autologous cell sources, high production costs, and lengthy manufacturing timelines. Our review underscores the need for continued research to facilitate broader clinical implementation of these therapies across diverse healthcare settings.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1737202","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:41:14Z","timestamp":1777527674000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Adapting CAR-T and CAR-Treg cancer therapies for autoimmunity: innovations and challenges"],"prefix":"10.3389","volume":"17","author":[{"given":"Michael D.","family":"Lovelace","sequence":"first","affiliation":[{"name":"Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St. Vincent\u2019s Centre for Applied Medical Research","place":["Sydney, NSW, Australia"]},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Barrett","sequence":"additional","affiliation":[{"name":"College of Medicine and Dentistry, James Cook University","place":["Townsville, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Thomas","family":"Broome","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet","place":["Solna, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saparna","family":"Pai","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University","place":["Cairns, QLD, Australia"]},{"name":"TAARA Therapeutic Pty Ltd","place":["Cairns, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol32030122","article-title":"HPV and cervical cancer-biology, prevention, and treatment updates","volume":"32","author":"Wloszek","year":"2025","journal-title":"Curr Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2020.10.003","article-title":"Hepatitis C virus associated hepatocellular carcinoma","volume":"149","author":"Khatun","year":"2021","journal-title":"Adv Cancer Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1342455","article-title":"Targeting latent viral infection in EBV-associated lymphomas","volume":"15","author":"Kong","year":"2024","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-02145-1","article-title":"Viral and cellular oncogenes promote immune evasion","volume":"41","author":"Roetman","year":"2022","journal-title":"Oncogene"},{"key":"B5","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41392-025-02197-9","article-title":"Viral oncogenesis in cancer: from mechanisms to therapeutics","volume":"10","author":"Xiao","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01225-1","article-title":"TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers","volume":"27","author":"Nagarsheth","year":"2021","journal-title":"Nat Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.9093","article-title":"Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells","volume":"33","author":"Stevanovi\u0107","year":"2015","journal-title":"J Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.127","article-title":"Adoptive cellular immunotherapy for virus-associated cancers: a new paradigm in personalized medicine","volume":"95","author":"Smith","year":"2017","journal-title":"Immunol Cell Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00198-24","article-title":"Adoptive T-cell therapy for virus-associated diseases","volume":"38","author":"Smith","year":"2025","journal-title":"Clin Microbiol Rev"},{"key":"B10","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1038\/s41467-020-19505-2","article-title":"The once and future gene therapy","volume":"11","author":"Bulaklak","year":"2020","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-019-0074-7","article-title":"Delivering cellular and gene therapies to patients: solutions for realizing the potential of the next generation of medicine","volume":"27","author":"Elverum","year":"2020","journal-title":"Gene Ther"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0064-8","article-title":"Engineered immune cells as highly sensitive cancer diagnostics","volume":"37","author":"Aalipour","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/14653240701883087","article-title":"T-cell receptor gene transfer for treatment of leukemia","volume":"10","author":"Heemskerk","year":"2008","journal-title":"Cytotherapy"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00476-6","article-title":"Engineering the next generation of cell-based therapeutics","volume":"21","author":"Bashor","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B15","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/s12032-023-02146-y","article-title":"Revolutionizing cancer treatment: a comprehensive review of CAR-T cell therapy","volume":"40","author":"Dabas","year":"2023","journal-title":"Med Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1709919","article-title":"Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia","volume":"378","author":"Park","year":"2018","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00910-5","article-title":"Recent advances in CAR-T cell engineering","volume":"13","author":"Huang","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08171-9","article-title":"Intravenous and intracranial GD2-CAR T cells for H3K27M+ diffuse midline gliomas","volume":"637","author":"Monje","year":"2025","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02875-1","article-title":"Locoregional delivery of IL-13R\u03b12-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial","volume":"30","author":"Brown","year":"2024","journal-title":"Nat Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ado9371","article-title":"CAR T cells based on fully human T cell receptor-mimetic antibodies exhibit potent antitumor activity in vivo","volume":"17","author":"Salzler","year":"2025","journal-title":"Sci Transl Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1177\/15330338231204198","article-title":"Current situation and prospect of adoptive cellular immunotherapy for Malignancies","volume":"22","author":"Zhao","year":"2023","journal-title":"Technol Cancer Res Treat"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlife.2024.05.005","article-title":"BCMA-CD19 bispecific CAR-T therapy in refractory chronic inflammatory demyelinating polyneuropathy","volume":"2","author":"Zhang","year":"2024","journal-title":"hLife"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.154","article-title":"Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia","volume":"21","author":"Ritchie","year":"2013","journal-title":"Mol Ther"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1615212","article-title":"Tracing the development of CAR-T cell design: from concept to next-generation platforms","volume":"16","author":"Alsaieedi","year":"2025","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj6251","article-title":"Enhancing the safety of CAR-T cell therapy: synthetic genetic switch for spatiotemporal control","volume":"10","author":"Lu","year":"2024","journal-title":"Sci Adv"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01637-z","article-title":"Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells","volume":"41","author":"Oh","year":"2023","journal-title":"Nat Biotechnol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.clim.2013.11.004","article-title":"Use of gene-modified regulatory T-cells to control autoimmune and alloimmune pathology: is now the right time","volume":"150","author":"Jethwa","year":"2014","journal-title":"Clin Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/ni0901-816","article-title":"Regulatory T cells in the control of immune pathology","volume":"2","author":"Maloy","year":"2001","journal-title":"Nat Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070590","article-title":"A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism","volume":"204","author":"Coombes","year":"2007","journal-title":"J Exp Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/978-981-15-6407-9_15","article-title":"Regulatory T cells for the induction of transplantation tolerance","volume":"1278","author":"Que","year":"2021","journal-title":"Adv Exp Med Biol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065x.2006.00428.x","article-title":"Immune privilege induced by regulatory T cells in transplantation tolerance","volume":"213","author":"Cobbold","year":"2006","journal-title":"Immunol Rev"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.2.287","article-title":"CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production","volume":"188","author":"Thornton","year":"1998","journal-title":"J Exp Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1365-2567.2008.02813.x","article-title":"Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target","volume":"124","author":"Sojka","year":"2008","journal-title":"Immunology"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/ni1428","article-title":"Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice","volume":"8","author":"Kim","year":"2007","journal-title":"Nat Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1172\/jci82771","article-title":"Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor","volume":"126","author":"MacDonald","year":"2016","journal-title":"J Clin Invest"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.747143","article-title":"Crosstalk of microorganisms and immune responses in autoimmune neuroinflammation: a focus on regulatory T cells","volume":"12","author":"Schroeter","year":"2021","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1075813","article-title":"The emerging role of regulatory cell-based therapy in autoimmune disease","volume":"13","author":"Ghobadinezhad","year":"2022","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1613622","article-title":"CAR-based cell therapy for autoimmune diseases","volume":"16","author":"Li","year":"2025","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-04-566786","article-title":"Engineered antigen-specific human regulatory T cells: immunosuppression of FVIII-specific T- and B-cell responses","volume":"125","author":"Kim","year":"2015","journal-title":"Blood"},{"key":"B40","doi-asserted-by":"publisher","first-page":"14030","DOI":"10.1038\/mtm.2014.30","article-title":"Ex vivo expanded autologous polyclonal regulatory T cells suppress inhibitor formation in hemophilia","volume":"1","author":"Sarkar","year":"2014","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1177\/11786469241248287","article-title":"A review of the evidence for tryptophan and the kynurenine pathway as a regulator of stem cell niches in health and disease","volume":"17","author":"Summers","year":"2024","journal-title":"Int J Tryptophan Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s40164-025-00715-7","article-title":"Chimeric antigen receptor modified hematopoietic stem cells (CAR-HSCs) arm all immune forces for anti-tumor in mice","volume":"14","author":"Wang","year":"2025","journal-title":"Exp Hematol Oncol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2024.101250","article-title":"CAR-T cell manufacturing landscape-lessons from the past decade and considerations for early clinical development","volume":"32","author":"Dias","year":"2024","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1084\/jem.20230903","article-title":"CAR-T cell manufacturing: major process parameters and next-generation strategies","volume":"221","author":"Melanie Ayala Ceja","year":"2024","journal-title":"J\u00a0Exp Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.37765\/ajmc.2023.89391","article-title":"The role of automation in meeting the growing demand for CAR T-cell therapies","volume":"29","author":"Tomtishen","year":"2023","journal-title":"Am J Manag Care"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.968395","article-title":"CAR-T cell\u00a0development for cutaneous T cell lymphoma: current limitations and potential\u00a0treatment strategies","volume":"13","author":"To","year":"2022","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adr9382","article-title":"Chimeric antigen receptor T cells against the IGHV4\u201334 B cell receptor specifically eliminate neoplastic and autoimmune B cells","volume":"18","author":"Cohen","year":"2026","journal-title":"Sci Transl Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-761320","article-title":"CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell Malignancies","volume":"130","author":"Gomes-Silva","year":"2017","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1056\/nejmoa2300709","article-title":"Base-edited CAR7 T cells for relapsed T-cell acute lymphoblastic leukemia","volume":"389","author":"Chiesa","year":"2023","journal-title":"N Engl J Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2022.02.013","article-title":"Feasibility study of a novel preparation strategy for anti-CD7 CAR-T cells with a recombinant anti-CD7 blocking antibody","volume":"24","author":"Ye","year":"2022","journal-title":"Mol Ther Oncolytics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1038\/s41419-018-0918-x","article-title":"The biological basis and clinical symptoms of CAR-T therapy-associated toxicites","volume":"9","author":"Titov","year":"2018","journal-title":"Cell Death Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","article-title":"Chimeric antigen receptor T-cell therapy - assessment and management of toxicities","volume":"15","author":"Neelapu","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jim.2016.03.005","article-title":"Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and\/or siltuximab following CAR T cell therapy","volume":"434","author":"Chen","year":"2016","journal-title":"J Immunol Methods"},{"key":"B54","volume-title":"Chimeric Antigen Receptor T-Cell Therapies for Cancer: A Practical Guide","author":"Lee","year":"2020"},{"key":"B55","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41577-021-00547-6","article-title":"Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy","volume":"22","author":"Morris","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1447147","article-title":"CAR-engineered T cell therapy as an emerging strategy for treating autoimmune diseases","volume":"11","author":"Vukovic","year":"2024","journal-title":"Front Med (Lausanne)"},{"key":"B57","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1056\/NEJMoa2308917","article-title":"CD19 CAR T-cell therapy in autoimmune disease - A case series with follow-up","volume":"390","author":"Muller","year":"2024","journal-title":"N Engl J Med"},{"key":"B58","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.blre.2018.11.002","article-title":"Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management","volume":"34","author":"Brudno","year":"2019","journal-title":"Blood Rev"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0285-8","article-title":"CAR T-cells for T-cell Malignancies: challenges in distinguishing between therapeutic, normal, and neoplastic T-cells","volume":"32","author":"Alcantara","year":"2018","journal-title":"Leukemia"},{"key":"B60","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.jcyt.2016.04.003","article-title":"Myeloid cells in peripheral blood mononuclear cell concentrates inhibit the expansion of chimeric antigen receptor T cells","volume":"18","author":"Stroncek","year":"2016","journal-title":"Cytotherapy"},{"key":"B61","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.1038\/s41467-022-30896-2","article-title":"Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing","volume":"13","author":"Jo","year":"2022","journal-title":"Nat Commun"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.omton.2024.200814","article-title":"Rejection resistant CD30.CAR-modified Epstein-Barr virus-specific T cells as an off-the-shelf platform for CD30(+) lymphoma","volume":"32","author":"Quach","year":"2024","journal-title":"Mol Ther Oncol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01272","article-title":"Virus-specific T cells for the immunocompromised patient","volume":"8","author":"Houghtelin","year":"2017","journal-title":"Front Immunol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1186\/s12967-019-1988-y","article-title":"A strategy to protect off-the-shelf cell therapy products using virus-specific T-cells engineered to eliminate alloreactive T-cells","volume":"17","author":"Quach","year":"2019","journal-title":"J Transl Med"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"B66","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41467-020-20658-3","article-title":"A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy","volume":"12","author":"Iriguchi","year":"2021","journal-title":"Nat Commun"},{"key":"B67","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40364-022-00359-3","article-title":"Donor T cells for CAR T cell therapy","volume":"10","author":"Tang","year":"2022","journal-title":"biomark Res"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph191912366","article-title":"Price and prejudice? The value of chimeric antigen receptor (CAR) T-cell therapy","volume":"19","author":"Choi","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-013518","article-title":"Enabling access to genetically modified cell therapies through flexible approaches to manufacturing and cost recovery","volume":"13","author":"Stewart","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B70","doi-asserted-by":"publisher","first-page":"102289","DOI":"10.1016\/j.jaut.2019.05.017","article-title":"Regulatory T cells engineered with a novel insulin-specific chimeric antigen receptor as a candidate immunotherapy for type 1 diabetes","volume":"103","author":"Tenspolde","year":"2019","journal-title":"J Autoimmun"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1613878","article-title":"CAR T-cell therapy in autoimmune diseases: a promising frontier on the horizon","volume":"16","author":"Wu","year":"2025","journal-title":"Front Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-025-09113-7","article-title":"CAR T cell therapy for rheumatoid arthritis","volume":"68","author":"Freeley","year":"2025","journal-title":"Clin Rev Allergy Immunol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/978-3-030-24436-1_6","article-title":"Multiple sclerosis","volume":"403","author":"Jakimovski","year":"2024","journal-title":"Lancet"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-010-0216-x","article-title":"Knocking at the brain's door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures","volume":"32","author":"Kawakami","year":"2010","journal-title":"Semin Immunopathol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526065","article-title":"Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis","volume":"35","author":"Haas","year":"2005","journal-title":"Eur J Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2007.00064.x","article-title":"The immunopathology of multiple sclerosis: an overview","volume":"17","author":"Lassmann","year":"2007","journal-title":"Brain Pathol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2020.102401","article-title":"Treatment of experimental autoimmune encephalomyelitis with engineered bi-specific Foxp3+ regulatory CD4+ T cells","volume":"108","author":"Malviya","year":"2020","journal-title":"J Autoimmun"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200839073","article-title":"Curing CNS autoimmune disease with myelin-reactive Foxp3+ Treg","volume":"39","author":"Stephens","year":"2009","journal-title":"Eur J Immunol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneuro0832","article-title":"The role of regulatory T cells in multiple sclerosis","volume":"4","author":"Zozulya","year":"2008","journal-title":"Nat Clin Pract Neurol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.81","article-title":"Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT","volume":"21","author":"Muraro","year":"2025","journal-title":"Nat Rev Neurol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.70131","article-title":"Autologous hematopoietic stem cell transplantation in systemic sclerosis: current evidence and future directions","volume":"7","author":"Sieiro Santos","year":"2025","journal-title":"ACR Open Rheumatol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516645670","article-title":"NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs","volume":"23","author":"Sormani","year":"2017","journal-title":"Mult Scler"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000003987","article-title":"Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta-analysis","volume":"88","author":"Sormani","year":"2017","journal-title":"Neurology"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.18743","article-title":"Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis: A randomized clinical trial","volume":"321","author":"Burt","year":"2019","journal-title":"JAMA"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000011461","article-title":"Long-term clinical outcomes of hematopoietic stem cell transplantation in multiple sclerosis","volume":"96","author":"Boffa","year":"2021","journal-title":"Neurology"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1172\/jci71691","article-title":"T cell repertoire following autologous stem cell transplantation for multiple sclerosis","volume":"124","author":"Muraro","year":"2014","journal-title":"J Clin Invest"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.5867","article-title":"Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis","volume":"74","author":"Muraro","year":"2017","journal-title":"JAMA Neurol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.798300","article-title":"Haematopoietic stem cell transplantation results in extensive remodelling of the clonal T cell repertoire in multiple sclerosis","volume":"13","author":"Massey","year":"2022","journal-title":"Front Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51510","article-title":"Sustained immunotolerance in multiple sclerosis after stem cell transplant","volume":"9","author":"Visweswaran","year":"2022","journal-title":"Ann Clin Transl Neurol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000200027","article-title":"B-cell reconstitution after autologous hematopoietic stem cell transplantation in multiple sclerosis","volume":"9","author":"von Niederhausern","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.0676","article-title":"Interpreting lymphocyte reconstitution data from the pivotal phase 3 trials of alemtuzumab","volume":"74","author":"Baker","year":"2017","journal-title":"JAMA Neurol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.molmed.2019.11.003","article-title":"Epstein-barr virus in multiple sclerosis: theory and emerging immunotherapies","volume":"26","author":"Bar-Or","year":"2020","journal-title":"Trends Mol Med"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.1178","article-title":"Potential clinical implications of molecular mimicry-induced autoimmunity","volume":"12","author":"Suliman","year":"2024","journal-title":"Immun Inflammation Dis"},{"key":"B94","doi-asserted-by":"publisher","first-page":"9403","DOI":"10.1038\/s41467-024-53658-8","article-title":"Molecular mimicry as a mechanism of viral immune evasion and autoimmunity","volume":"15","author":"Maguire","year":"2024","journal-title":"Nat Commun"},{"key":"B95","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41579-022-00770-5","article-title":"Epstein-Barr virus and multiple sclerosis","volume":"21","author":"Soldan","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1444","article-title":"Adoptive T-cell therapy targeting Epstein-Barr virus as a treatment for multiple sclerosis","volume":"12","author":"Smith","year":"2023","journal-title":"Clin Transl Immunol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124714","article-title":"Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis","volume":"3","author":"Pender","year":"2018","journal-title":"JCI Insight"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000200094","article-title":"Association of higher ocrelizumab exposure with reduced disability progression in multiple sclerosis","volume":"10","author":"Hauser","year":"2023","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000045698","article-title":"Advances and prospects of CAR-T cell therapy in autoimmune disease treatment","volume":"104","author":"Wang","year":"2025","journal-title":"Med (Baltimore)"},{"key":"B100","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.medj.2024.03.002","article-title":"CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis","volume":"5","author":"Fischbach","year":"2024","journal-title":"Med"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0254-y","article-title":"The heterogeneous pathogenesis of type 1 diabetes mellitus","volume":"15","author":"Ilonen","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1172\/jci94549","article-title":"Autoreactive T cells in type 1 diabetes","volume":"127","author":"Pugliese","year":"2017","journal-title":"J Clin Invest"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.08.007","article-title":"Immune and pancreatic \u03b2 cell interactions in type 1 diabetes","volume":"27","author":"Boldison","year":"2016","journal-title":"Trends Endocrinol Metab"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1440045","article-title":"Antigen-specific T cell responses in autoimmune diabetes","volume":"15","author":"Dwyer","year":"2024","journal-title":"Front Immunol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0516","article-title":"Natural variation in interleukin-2 sensitivity influences regulatory T-cell frequency and function in individuals with long-standing type 1 diabetes","volume":"64","author":"Yang","year":"2015","journal-title":"Diabetes"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100272","article-title":"Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function","volume":"188","author":"Garg","year":"2012","journal-title":"J Immunol"},{"key":"B107","doi-asserted-by":"publisher","first-page":"8359683","DOI":"10.1155\/2024\/8359683","article-title":"Evidence for molecular mimicry between SARS-CoV-2 and human antigens: Implications for autoimmunity in COVID-19","volume":"2024","author":"Ar\u00e9valo-Cort\u00e9s","year":"2024","journal-title":"Autoimmune Dis"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3390\/v15030782","article-title":"The role of viral infections in the onset of autoimmune diseases","volume":"15","author":"Sundaresan","year":"2023","journal-title":"Viruses"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1326711","article-title":"Immunological and virological triggers of type 1 diabetes: Insights and implications","volume":"14","author":"Lemos","year":"2023","journal-title":"Front Immunol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1177\/1179551419844521","article-title":"Therapies for type 1 diabetes: Current scenario and future perspectives","volume":"12","author":"Pathak","year":"2019","journal-title":"Clin Med Insights Endocrinol Diabetes"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-025-02150-8","article-title":"Emerging immunotherapies for disease modification of type 1 diabetes","volume":"85","author":"Foster","year":"2025","journal-title":"Drugs"},{"key":"B112","doi-asserted-by":"publisher","first-page":"18","DOI":"10.20517\/mtod.2024.52","article-title":"Regulatory T cell-based therapies for type 1 diabetes: A narrative review","volume":"5","author":"Velikova","year":"2025","journal-title":"Metab Target Organ Damage"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.635767","article-title":"Emerging\u00a0therapeutic strategies to restore regulatory T cell control of islet autoimmunity in type 1 diabetes","volume":"12","author":"Volfson-Sedletsky","year":"2021","journal-title":"Front Immunol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay6422","article-title":"Gene editing to induce FOXP3 expression in human CD4(+) T cells leads to a stable regulatory phenotype and function","volume":"12","author":"Honaker","year":"2020","journal-title":"Sci Transl Med"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402739","article-title":"Therapeutic regulatory T cells subvert effector T cell function in inflamed islets to halt autoimmune diabetes","volume":"194","author":"Mahne","year":"2015","journal-title":"J Immunol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1463971","article-title":"Regulatory CD4(+) T cells redirected against pathogenic CD8(+) T cells protect NOD mice from development of autoimmune diabetes","volume":"15","author":"Kakabadse","year":"2024","journal-title":"Front Immunol"},{"key":"B117","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 Transl Med"},{"key":"B118","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.clim.2014.03.016","article-title":"Therapy of type 1 diabetes with CD4(+)CD25(high)CD127-regulatory T cells prolongs survival of pancreatic islets - results of one year follow-up","volume":"153","author":"Marek-Trzonkowska","year":"2014","journal-title":"Clin Immunol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147474","article-title":"The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes","volume":"6","author":"Dong","year":"2021","journal-title":"JCI Insight"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2019.03.041","article-title":"Conjugation of a peptide autoantigen to gold nanoparticles for intradermally administered antigen specific immunotherapy","volume":"562","author":"Dul","year":"2019","journal-title":"Int J Pharm"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1038\/nature16962","article-title":"Expanding antigen-specific regulatory networks to treat autoimmunity","volume":"530","author":"Clemente-Casares","year":"2016","journal-title":"Nature"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aad0612","article-title":"Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2","volume":"9","author":"Yeste","year":"2016","journal-title":"Sci Signal"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1207108","article-title":"Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes","volume":"14","author":"Obarorakpor","year":"2023","journal-title":"Front Immunol"},{"key":"B124","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":"B125","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2012495117","article-title":"A biomimetic five-module chimeric antigen receptor ((5M)CAR) designed to target and eliminate antigen-specific T cells","volume":"117","author":"Kobayashi","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-011-2179-4","article-title":"Adoptive cell therapy using antigen-specific CD4\u2212CD8\u2212T regulatory cells to prevent autoimmune diabetes and promote islet allograft survival in NOD mice","volume":"54","author":"Zhang","year":"2011","journal-title":"Diabetologia"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.694118","article-title":"Hematopoietic stem cells in type 1 diabetes","volume":"12","author":"Pastore","year":"2021","journal-title":"Front Immunol"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00167","article-title":"Immunological balance is associated with clinical outcome after autologous hematopoietic stem cell transplantation in type 1 diabetes","volume":"8","author":"Malmegrim","year":"2017","journal-title":"Front Immunol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2017.12.006","article-title":"Clinical benefits of autologous haematopoietic stem cell transplantation in type 1 diabetes patients","volume":"44","author":"Gu","year":"2018","journal-title":"Diabetes Metab"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.07.020","article-title":"Lack of persistent remission following initial recovery in patients with type 1 diabetes treated with autologous peripheral blood stem cell transplantation","volume":"143","author":"Walicka","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/j.deman.2024.100247","article-title":"Innovative immunotherapies and emerging treatments in type 1 diabetes management","volume":"17","author":"Zarei","year":"2025","journal-title":"Diabetes Epidemiol Manage"},{"key":"B132","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13287-024-03636-0","article-title":"Current status of stem cell therapy for type 1 diabetes: A critique and a prospective consideration","volume":"15","author":"Ghoneim","year":"2024","journal-title":"Stem Cell Res Ther"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.631463","article-title":"Stem cell-based clinical trials for diabetes mellitus","volume":"12","author":"de Klerk","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.ej12-0343","article-title":"Long term effects of the implantation of Wharton's jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus","volume":"60","author":"Hu","year":"2013","journal-title":"Endocr J"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0656","article-title":"Preserved \u03b2-cell function in type 1 diabetes by mesenchymal stromal cells","volume":"64","author":"Carlsson","year":"2015","journal-title":"Diabetes"},{"key":"B136","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41409-024-02429-6","article-title":"CAR-T cell therapy embarks on autoimmune disease","volume":"60","author":"Rampotas","year":"2025","journal-title":"Bone Marrow Transplant"},{"key":"B137","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.jaci.2024.12.1066","article-title":"Chimeric antigen receptor-modified T-cell therapy: Recent updates and challenges in autoimmune diseases","volume":"155","author":"Ca\u00ebl","year":"2025","journal-title":"J\u00a0Allergy Clin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1737202\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:41:16Z","timestamp":1777527676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1737202\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":137,"alternative-id":["10.3389\/fimmu.2026.1737202"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1737202","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"article-number":"1737202"}}