B cell targeted CAR-T therapy for autoimmune diseases

Abstract

Chimeric antigen receptor T (CAR-T) cells demonstrate remarkable effectiveness in targeting and eliminating pathogenic B-cell lineages, showing significant specificity and efficacy against B cell malignancies. In addition, CAR-T cell-mediated B cell depletion and resetting, which showed great potential in treating autoimmune diseases, thereby extending the clinical applicability of adoptive cell therapy. In this review, we examine the progression of CAR-T targeted B cell therapy for autoimmune diseases, encompassing the development of new therapeutic strategies and reports on related clinical outcomes. Furthermore, the article delves into the challenges and potential avenues for enhancement related to the safety aspects and inherent limitations of current technological solutions.

Keywords

chimeric antigen receptor-T therapy / autoimmune diseases / clinical application / lymphodepletion / systemic lupus erythematosus / multiple sclerosis / rheumatoid arthritis / myasthenia gravis / immune-mediated necrotizing myopathy / systemic sclerosis

References

[1] Pisetsky DS . Pathogenesis of autoimmune disease. Nat Rev Nephrol 2023; 19(8): 509–524

[2] Berry CT , Frazee CS , Herman PJ , Chen S , Chen A , Kuo Y , Ellebrecht CT . Current advancements in cellular immunotherapy for autoimmune disease. Semin Immunopathol 2025; 47(1): 7

[3] Abeles I , Palma C , Meednu N , Payne AS , Looney RJ , Anolik JHB . Cell-directed therapy in autoimmunity. Annu Rev Immunol 2024; 42(1): 103–126

[4] Lee DSW , Rojas OL , Gommerman JL . B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat Rev Drug Discov 2021; 20(3): 179–199

[5] Urbonaviciute V , Fürnrohr BG , Meister S , Munoz L , Heyder P , De Marchis F , Bianchi ME , Kirschning C , Wagner H , Manfredi AA , Kalden JR , Schett G , Rovere-Querini P , Herrmann M , Voll RE . Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med 2008; 205(13): 3007–3018

[6] Schett G , June CH . CAR T cells in autoimmune disease: on the road to remission. Immunity 2024; 57(12): 2705–2709

[7] Sanz I , Wei C , Jenks SA , Cashman KS , Tipton C , Woodruff MC , Hom J , Lee FE . Challenges and opportunities for consistent classification of human B cell and plasma cell populations. Front Immunol 2019; 10: 2458

[8] Kaminski DA , Wei C , Qian Y , Rosenberg AF , Sanz I . Advances in human B cell phenotypic profiling. Front Immunol 2012; 3: 302

[9] Israel E , Kapelushnik J , Yermiahu T , Levi I , Yaniv I , Shpilberg O , Shubinsky G . Expression of CD24 on CD19^–CD79a⁺ early B-cell progenitors in human bone marrow. Cell Immunol 2005; 236(1-2): 171–178

[10] Pavlasova G , Mraz M . The regulation and function of CD20: an “enigma” of B-cell biology and targeted therapy. Haematologica 2020; 105(6): 1494–1506

[11] Monzón-Casanova E , Matheson LS , Tabbada K , Zarnack K , Smith CW , Turner M . Polypyrimidine tract-binding proteins are essential for B cell development. Elife 2020; 9: e5355

[12] Ren A , Sun J , Yin W , Westerberg LS , Miller H , Lee P , Candotti F , Guan F , Lei J , Gong Q , Chen Y , Liu C . Signaling networks in B cell development and related therapeutic strategies. J Leukoc Biol 2022; 111(4): 877–891

[13] Saberi Hosnijeh F , Kolijn PM , Casabonne D , Nieters A , Solans M , Naudin S , Ferrari P , Mckay JD , Weiderpass E , Perduca V , Besson C , Mancini FR , Masala G , Krogh V , Ricceri F , Huerta JM , Petrova D , Sala N , Trichopoulou A , Karakatsani A , La Vecchia C , Kaaks R , Canzian F , Aune D , Boeing H , Schulze MB , Perez-Cornago A , Langerak AW , van der Velden VHJ , Vermeulen R . Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development. Sci Rep 2020; 10(1): 13814

[14] Syeda MZ , Hong T , Huang C , Huang W , Mu Q . B cell memory: from generation to reactivation: a multipronged defense wall against pathogens. Cell Death Discov 2024; 10(1): 117

[15] Horna P , Nowakowski G , Endell J , Boxhammer R . Comparative assessment of surface CD19 and CD20 expression on B-cell lymphomas from clinical biopsies: implications for targeted therapies. Blood 2019; 134(Supplement_1): 5345

[16] Choudhry P , Mariano MC , Geng H , Martin TG III , Wolf JL , Wong SW , Shah N , Wiita AP . DNA methyltransferase inhibitors upregulate CD38 protein expression and enhance daratumumab efficacy in multiple myeloma. Leukemia 2020; 34(3): 938–941

[17] Beers SA , Chan CH , French RR , Cragg MS , Glennie MJ . CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol 2010; 47(2): 107–114

[18] McLaughlin P , Grillo-López AJ , Link BK , Levy R , Czuczman MS , Williams ME , Heyman MR , Bence-Bruckler I , White CA , Cabanillas F , Jain V , Ho AD , Lister J , Wey K , Shen D , Dallaire BK . Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998; 16(8): 2825–2833

[19] Gelfand JM , Cree BAC , Hauser SL . Ocrelizumab and other CD20⁺ B-cell-depleting therapies in multiple sclerosis. Neurotherapeutics 2017; 14(4): 835–841

[20] Kappos L , Li D , Calabresi PA , O’Connor P , Bar-Or A , Barkhof F , Yin M , Leppert D , Glanzman R , Tinbergen J , Hauser SL . Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet 2011; 378(9805): 1779–1787

[21] Forsthuber TG , Cimbora DM , Ratchford JN , Katz E , Stüve O . B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets. Ther Adv Neurol Disord 2018; 11: 1756286418761697

[22] Parker KR , Migliorini D , Perkey E , Yost KE , Bhaduri A , Bagga P , Haris M , Wilson NE , Liu F , Gabunia K , Scholler J , Montine TJ , Bhoj VG , Reddy R , Mohan S , Maillard I , Kriegstein AR , June CH , Chang HY , Posey AD Jr , Satpathy AT . Single-cell analyses identify brain mural cells expressing CD19 as potential off-tumor targets for CAR-T immunotherapies. Cell 2020; 183(1): 126–142.e17

[23] Morris EC , Neelapu SS , Giavridis T , Sadelain M . Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol 2022; 22(2): 85–96

[24] Madry C , Laabi Y , Callebaut I , Roussel J , Hatzoglou A , Le Coniat M , Mornon JP , Berger R , Tsapis A . The characterization of murine BCMA gene defines it as a new member of the tumor necrosis factor receptor superfamily. Int Immunol 1998; 10(11): 1693–1702

[25] Coquery CM , Erickson LD . Regulatory roles of the tumor necrosis factor receptor BCMA. Crit Rev Immunol 2012; 32(4): 287–305

[26] Thompson JS , Schneider P , Kalled SL , Wang LC , Lefevre EA , Cachero TG , MacKay F , Bixler SA , Zafari M , Liu ZY , Woodcock SA , Qian F , Batten M , Madry C , Richard Y , Benjamin CD , Browning JL , Tsapis A , Tschopp J , Ambrose C . BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population. J Exp Med 2000; 192(1): 129–136

[27] Sasaki Y , Casola S , Kutok JL , Rajewsky K , Schmidt-Supprian M . TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology. J Immunol 2004; 173(4): 2245–2252

[28] Qin C , Tian DS , Zhou LQ , Shang K , Huang L , Dong MH , You YF , Xiao J , Xiong Y , Wang W , Pang H , Guo JJ , Cai SB , Wang D , Li CR , Zhang M , Bu BT , Wang W . Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results. Signal Transduct Target Ther 2023; 8(1): 5

[29] Ye X , Zhao Y , Ma W , Ares I , Martínez M , Lopez-Torres B , Martínez-Larrañaga MR , Wang X , Anadón A , Martínez MA . The potential of CD38 protein as a target for autoimmune diseases. Autoimmun Rev 2023; 22(4): 103289

[30] Clark EA , Giltiay NV . CD22: a regulator of innate and adaptive B cell responses and autoimmunity. Front Immunol 2018; 9: 2235

[31] Raman VS , Bal V , Rath S , George A . Ligation of CD27 on murine B cells responding to T-dependent and T-independent stimuli inhibits the generation of plasma cells. J Immunol 2000; 165(12): 6809–6815

[32] Bryl E . B cells as target for immunotherapy in rheumatic diseases-current status. Immunol Lett 2021; 236: 12–19

[33] Wang W , He S , Zhang W , Zhang H , DeStefano VM , Wada M , Pinz K , Deener G , Shah D , Hagag N , Wang M , Hong M , Zeng R , Lan T , Ma Y , Li F , Liang Y , Guo Z , Zou C , Wang M , Ding L , Ma Y , Yuan Y . BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial. Ann Rheum Dis 2024; 83(10): 1304–1314

[34] Roddie C , O’Reilly M , Dias Alves Pinto J , Vispute K , Lowdell M . Manufacturing chimeric antigen receptor T cells: issues and challenges. Cytotherapy 2019; 21(3): 327–340

[35] Gomes-Silva D , Ramos CA . Cancer immunotherapy using CAR-T cells: from the research bench to the assembly Line. Biotechnol J 2018; 13(2): 1–1

[36] Lin JK , Muffly LS , Spinner MA , Barnes JI , Owens DK , Goldhaber-Fiebert JD . Cost effectiveness of chimeric antigen receptor T-cell therapy in multiply relapsed or refractory adult large B-cell lymphoma. J Clin Oncol 2019; 37(24): 2105–2119

[37] Zhao J , Lin Q , Song Y , Liu D . Universal CARs, universal T cells, and universal CAR T cells. J Hematol Oncol 2018; 11(1): 132

[38] Qasim W , Zhan H , Samarasinghe S , Adams S , Amrolia P , Stafford S , Butler K , Rivat C , Wright G , Somana K , Ghorashian S , Pinner D , Ahsan G , Gilmour K , Lucchini G , Inglott S , Mifsud W , Chiesa R , Peggs KS , Chan L , Farzeneh F , Thrasher AJ , Vora A , Pule M , Veys P . Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med 2017; 9(377): aam9292

[39] Buckner JH . Mechanisms of impaired regulation by CD4⁺CD25⁺FOXP3⁺ regulatory T cells in human autoimmune diseases. Nat Rev Immunol 2010; 10(12): 849–859

[40] Bluestone JA , Auchincloss H , Nepom GT , Rotrosen D . Clair EW, Turka LA. The immune tolerance network at 10 years: tolerance in the age of immunotherapy. Nat Rev Immunol 2010; 10(11): 798–803

[41] Shin JH , Park HB , Oh DY . et al. Eliminating pathogenic T cells via gene-edited universal CAR-T cells: a novel strategy for autoimmune diseases. Mol Ther 2023; 31(6): 1579–1592

[42] Xin T , Cheng L , Zhou C , Zhao Y , Hu Z , Wu X . In-vivo induced CAR-T cell for the potential breakthrough to overcome the barriers of current CAR-T cell therapy. Front Oncol 2022; 12: 809754

[43] Parayath NN , Stephan MT . In situ programming of CAR T cells. Annu Rev Biomed Eng 2021; 23(1): 385–405

[44] Chen Z , Hu Y , Mei H . Advances in CAR-engineered immune cell generation: engineering approaches and sourcing strategies. Adv Sci (Weinh) 2023; 10(35): 2303215

[45] Hirayama AV , Gauthier J , Hay KA , Voutsinas JM , Wu Q , Gooley T , Li D , Cherian S , Chen X , Pender BS , Hawkins RM , Vakil A , Steinmetz RN , Acharya UH , Cassaday RD , Chapuis AG , Dhawale TM , Hendrie PC , Kiem HP , Lynch RC , Ramos J , Shadman M , Till BG , Riddell SR , Maloney DG , Turtle CJ . The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells. Blood 2019; 133(17): 1876–1887

[46] Lickefett B , Chu L , Ortiz-Maldonado V , Warmuth L , Barba P , Doglio M , Henderson D , Hudecek M , Kremer A , Markman J , Nauerth M , Negre H , Sanges C , Staber PB , Tanzi R , Delgado J , Busch DH , Kuball J , Luu M , Jäger U . Lymphodepletion—an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle. Front Immunol 2023; 14: 1303935

[47] Porter DL , Hwang WT , Frey NV , Lacey SF , Shaw PA , Loren AW , Bagg A , Marcucci KT , Shen A , Gonzalez V , Ambrose D , Grupp SA , Chew A , Zheng Z , Milone MC , Levine BL , Melenhorst JJ , June CH . Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303): 303ra139

[48] Porter DL , Levine BL , Kalos M , Bagg A , June CH . Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2016; 374(10): 998

[49] Ritchie DS , Neeson PJ , Khot A , Peinert S , Tai T , Tainton K , Chen K , Shin M , Wall DM , Hönemann D , Gambell P , Westerman DA , Haurat J , Westwood JA , Scott AM , Kravets L , Dickinson M , Trapani JA , Smyth MJ , Darcy PK , Kershaw MH , Prince HM . Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 2013; 21(11): 2122–2129

[50] Shank BR , Do B , Sevin A , Chen SE , Neelapu SS , Horowitz SB . Chimeric antigen receptor T cells in hematologic malignancies. Pharmacotherapy 2017; 37(3): 334–345

[51] Schett G , Müller F , Taubmann J , Mackensen A , Wang W , Furie RA , Gold R , Haghikia A , Merkel PA , Caricchio R , D’Agostino MA , Locatelli F , June CH , Mougiakakos D . Advancements and challenges in CAR T cell therapy in autoimmune diseases. Nat Rev Rheumatol 2024; 20(9): 531–544

[52] Li P , Liu Y , Liang Y , Bo J , Gao S , Hu Y , Hu Y , Huang H , Huang X , Jing H , Ke X , Li J , Li Y , Liu Q , Lu P , Mei H , Niu T , Song Y , Song Y , Su L , Tu S , Wang J , Wu D , Wang Z , Xu K , Ying Z , Yang Q , Zhang Y , Shi F , Zhang B , Zhang H , Zhang X , Zhao M , Zhao W , Zhao X , Huang L , Zhu J , Qian W , Han W , Liang A . 2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma. Cancer Biol Med 2023; 20(2): 129–146

[53] Mohty M , Minnema MC . Lymphodepleting conditioning regimens. 2022; 131–133

[54] Chinese Society of Clinical Oncology. CSCO CAR-T Cell Therapy Guidelines for Hematologic Malignancies. Beijing: People’s Medical Publishing House, 2024

[55] Lin Y , Qiu L , Usmani S , Joo CW , Costa L , Derman B , Du J , Einsele H , Fernandez de Larrea C , Hajek R , Ho PJ , Kastritis E , Martinez-Lopez J , Mateos MV , Mikhael J , Moreau P , Nagarajan C , Nooka A , O'Dwyer M , Schjesvold F , Sidana S , van de Donk NW , Weisel K , Zweegman S , Raje N , Otero PR , Anderson LD Jr , Kumar S , Martin T; International Myeloma Working Group . Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: a report from the International Myeloma Working Group Immunotherapy Committee. Lancet Oncol 2024; 25(8): e374–e387

[56] Bupha-Intr O , Haeusler G , Chee L , Thursky K , Slavin M , Teh B . CAR-T cell therapy and infection: a review. Expert Rev Anti Infect Ther 2021; 19(6): 749–758

[57] Rahman A , Isenberg DA . Systemic lupus erythematosus. N Engl J Med 2008; 358(9): 929–939

[58] Mougiakakos D , Krönke G , Völkl S , Kretschmann S , Aigner M , Kharboutli S , Böltz S , Manger B , Mackensen A , Schett G . CD19-targeted CAR T cells in refractory systemic lupus erythematosus. N Engl J Med 2021; 385(6): 567–569

[59] Müller F , Taubmann J , Bucci L , Wilhelm A , Bergmann C , Völkl S , Aigner M , Rothe T , Minopoulou I , Tur C , Knitza J , Kharboutli S , Kretschmann S , Vasova I , Spoerl S , Reimann H , Munoz L , Gerlach RG , Schäfer S , Grieshaber-Bouyer R , Korganow AS , Farge-Bancel D , Mougiakakos D , Bozec A , Winkler T , Krönke G , Mackensen A , Schett G . CD19 CAR T-cell therapy in autoimmune disease—a case series with follow-up. N Engl J Med 2024; 390(8): 687–700

[60] Zhang W , Feng J , Cinquina A , Wang Q , Xu H , Zhang Q , Sun L , Chen Q , Xu L , Pinz K , Wada M , Jiang X , Ma Y , Zhang H . Treatment of systemic lupus erythematosus using BCMA-CD19 compound CAR. Stem Cell Rev Rep 2021; 17(6): 2120–2123

[61] Arjomandnejad M , Kopec AL , Keeler AM . CAR-T regulatory (CAR-Treg) cells: engineering and applications. Biomedicines 2022; 10(2): 287

[62] Solé-Marcé C , Moline T , Cortés-Hernández J . POS0463 reengineering chimeric antigen receptor T cells for targeted therapy of lupus nephritis. Ann Rheum Dis 2022; 81: 485–486

[63] Yang C , Sun C , Tan B , Hu C , Wan L , Wang C , Shi X , Qin J , Zhang N , Zheng B , Liu M , Lin J , Du B , Tong H . Allogeneic anti-CD19 CAR-T cells induce remission in refractory systemic lupus erythematosus. Cell Res 2025; 35(8): 607–609

[64] Dendrou CA , Fugger L , Friese MA . Immunopathology of multiple sclerosis. Nat Rev Immunol 2015; 15(9): 545–558

[65] Attfield KE , Jensen LT , Kaufmann M , Friese MA , Fugger L . The immunology of multiple sclerosis. Nat Rev Immunol 2022; 22(12): 734–750

[66] Wekerle H , Kojima K , Lannes-Vieira J , Lassmann H , Linington C . Animal models. Ann Neurol 1994; 36(S1 Suppl): S47–S53

[67] Palanichamy A , Apeltsin L , Kuo TC , Sirota M , Wang S , Pitts SJ , Sundar PD , Telman D , Zhao LZ , Derstine M , Abounasr A , Hauser SL , von Büdingen HC . Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis. Sci Transl Med 2014; 6(248): 248ra106

[68] Stern JN , Yaari G , Vander Heiden JA , Church G , Donahue WF , Hintzen RQ , Huttner AJ , Laman JD , Nagra RM , Nylander A , Pitt D , Ramanan S , Siddiqui BA , Vigneault F , Kleinstein SH , Hafler DA , O’Connor KC . B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Sci Transl Med 2014; 6(248): 248ra107

[69] Hauser SL , Bar-Or A , Comi G , Giovannoni G , Hartung HP , Hemmer B , Lublin F , Montalban X , Rammohan KW , Selmaj K , Traboulsee A , Wolinsky JS , Arnold DL , Klingelschmitt G , Masterman D , Fontoura P , Belachew S , Chin P , Mairon N , Garren H , Kappos L . Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 2017; 376(3): 221–234

[70] Fischbach F , Richter J , Pfeffer LK , Fehse B , Berger SC , Reinhardt S , Kuhle J , Badbaran A , Rathje K , Gagelmann N , Borie D , Seibel J , Ayuk F , Friese MA , Heesen C , Kröger N . CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med (N Y) 2024; 5(6): 550–558.e2

[71] Mullard A. CAR-T therapy for multiple sclerosis enters US trials for first time. Nature 2024; [Epub ahead of print] doi: 10.1038/d41586-024-00470-5

[72] Haghikia A , Schett G , Mougiakakos D . B cell-targeting chimeric antigen receptor T cells as an emerging therapy in neuroimmunological diseases. Lancet Neurol 2024; 23(6): 615–624

[73] Laurent L , Anquetil F , Clavel C , Ndongo-Thiam N , Offer G , Miossec P , Pasquali JL , Sebbag M , Serre G . IgM rheumatoid factor amplifies the inflammatory response of macrophages induced by the rheumatoid arthritis-specific immune complexes containing anticitrullinated protein antibodies. Ann Rheum Dis 2015; 74(7): 1425–1431

[74] Yanaba K , Bouaziz JD , Haas KM , Poe JC , Fujimoto M , Tedder TF . A regulatory B cell subset with a unique CD1d^hiCD5⁺ phenotype controls T cell-dependent inflammatory responses. Immunity 2008; 28(5): 639–650

[75] Teng YK , Levarht EW , Toes RE , Huizinga TW , van Laar JM . Residual inflammation after rituximab treatment is associated with sustained synovial plasma cell infiltration and enhanced B cell repopulation. Ann Rheum Dis 2009; 68(6): 1011–1016

[76] Gottenberg JE , Ravaud P , Bardin T , Cacoub P , Cantagrel A , Combe B , Dougados M , Flipo RM , Godeau B , Guillevin L , Loët XL , Hachulla E , Schaeverbeke T , Sibilia J , Baron G , Mariette X . Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry. Arthritis Rheum 2010; 62(9): 2625–2632

[77] Zhang B , Wang Y , Yuan Y , Sun J , Liu L , Huang D , Hu J , Wang M , Li S , Song W , Chen H , Zhou D , Zhang X . In vitro elimination of autoreactive B cells from rheumatoid arthritis patients by universal chimeric antigen receptor T cells. Ann Rheum Dis 2021; 80(2): 176–184

[78] Li Y , Li S , Zhao X , Sheng J , Xue L , Schett G , Shi C , Hu B , Wang X , Chen Z . Fourth-generation chimeric antigen receptor T-cell therapy is tolerable and efficacious in treatment-resistant rheumatoid arthritis. Cell Res 2025; 35(3): 220–223

[79] Mahler M , Miller FW , Fritzler MJ . Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev 2014; 13(4-5): 367–371

[80] Konitsioti AM , Prüss H , Laurent S , Fink GR , Heesen C , Warnke C . Chimeric antigen receptor T-cell therapy for autoimmune diseases of the central nervous system: a systematic literature review. J Neurol 2024; 271(10): 6526–6542

[81] Müller F , Boeltz S , Knitza J , Aigner M , Völkl S , Kharboutli S , Reimann H , Taubmann J , Kretschmann S , Rösler W , Manger B , Wacker J , Mougiakakos D , Jabari S , Schröder R , Uder M , Roemer F , Krönke G , Mackensen A , Schett G . CD19-targeted CAR T cells in refractory antisynthetase syndrome. Lancet 2023; 401(10379): 815–818

[82] Ohno R , Nakamura A . Advancing autoimmune Rheumatic disease treatment: CAR-T cell therapies—evidence, safety, and future directions. Semin Arthritis Rheum 2024; 67: 152479

[83] Lyu X , Gupta L , Tholouli E , Chinoy H . Chimeric antigen receptor T cell therapy: a new emerging landscape in autoimmune rheumatic diseases. Rheumatology (Oxford) 2024; 63(5): 1206–1216

[84] Pecher AC , Hensen L , Klein R , Schairer R , Lutz K , Atar D , Seitz C , Stanger A , Schneider J , Braun C , Schmidt M , Horger M , Bornemann A , Faul C , Bethge W , Henes J , Lengerke C . CD19-targeting CAR T cells for myositis and interstitial lung disease associated with antisynthetase syndrome. JAMA 2023; 329(24): 2154–2162

[85] Denton CP , Khanna D . Systemic sclerosis. Lancet 2017; 390(10103): 1685–1699

[86] Furue M , Mitoma C , Mitoma H , Tsuji G , Chiba T , Nakahara T , Uchi H , Kadono T . Pathogenesis of systemic sclerosis-current concept and emerging treatments. Immunol Res 2017; 65(4): 790–797

[87] Sobolewski P , Maślińska M , Wieczorek M , Łagun Z , Malewska A , Roszkiewicz M , Nitskovich R , Szymańska E , Walecka I . Systemic sclerosis-multidisciplinary disease: clinical features and treatment. Reumatologia 2019; 57(4): 221–233

[88] Sato S , Fujimoto M , Hasegawa M , Takehara K . Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells. Arthritis Rheum 2004; 50(6): 1918–1927

[89] Numajiri H , Kuzumi A , Fukasawa T , Ebata S , Yoshizaki-Ogawa A , Asano Y , Kazoe Y , Mawatari K , Kitamori T , Yoshizaki A , Sato S . B cell depletion inhibits fibrosis via suppression of profibrotic macrophage differentiation in a mouse model of systemic sclerosis. Arthritis Rheumatol 2021; 73(11): 2086–2095

[90] van Laar JM , Farge D , Sont JK , Naraghi K , Marjanovic Z , Larghero J , Schuerwegh AJ , Marijt EWA , Vonk MC , Schattenberg AV , Matucci-Cerinic M , Voskuyl AE , van de Loosdrecht AA , Daikeler T , Kötter I , Schmalzing M , Martin T , Lioure B , Weiner SM , Kreuter A , Deligny C , Durand JM , Emery P , Machold KP , Sarrot-Reynauld F , Warnatz K , Adoue DFP , Constans J , Tony HP , Del Papa N , Fassas A , Himsel A , Launay D , Lo Monaco A , Philippe P , Quéré I , Rich É , Westhovens R , Griffiths B , Saccardi R , van den Hoogen FH , Fibbe WE , Socié G , Gratwohl A , Tyndall A . Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA 2014; 311(24): 2490–2498

[91] Bergmann C , Müller F , Distler JHW , Györfi AH , Völkl S , Aigner M , Kretschmann S , Reimann H , Harrer T , Bayerl N , Boeltz S , Wirsching A , Taubmann J , Rösler W , Spriewald B , Wacker J , Atzinger A , Uder M , Kuwert T , Mackensen A , Schett G . Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells. Ann Rheum Dis 2023; 82(8): 1117–1120

[92] Auth J , Müller F , Völkl S , Bayerl N , Distler JHW , Tur C , Raimondo MG , Chenguiti Fakhouri S , Atzinger A , Coppers B , Eckstein M , Liphardt AM , Bäuerle T , Tascilar K , Aigner M , Kretschmann S , Wirsching A , Taubmann J , Hagen M , Györfi AH , Kharboutli S , Krickau T , Dees C , Spörl S , Rothe T , Harrer T , Bozec A , Grieshaber-Bouyer R , Fuchs F , Kuwert T , Berking C , Horch RE , Uder M , Mackensen A , Schett G , Bergmann C . CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series. Lancet Rheumatol 2025; 7(2): e83–e93

[93] Wang X , Wu X , Tan B , Zhu L , Zhang Y , Lin L , Xiao Y , Sun A , Wan X , Liu S , Liu Y , Ta N , Zhang H , Song J , Li T , Zhou L , Yin J , Ye L , Lu H , Hong J , Cheng H , Wang P , Li W , Chen J , Zhang J , Luo J , Huang M , Guo L , Pan X , Jin Y , Ye W , Dai L , Zhu J , Sun L , Zheng B , Li D , He Y , Liu M , Wu H , Du B , Xu H . Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis. Cell 2024; 187(18): 4890–4904.e9

[94] Gilhus NE . Myasthenia Gravis. N Engl J Med 2016; 375(26): 2570–2581

[95] Gilhus NE , Verschuuren JJ . Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 2015; 14(10): 1023–1036

[96] Verschuuren JJ , Palace J , Murai H , Tannemaat MR , Kaminski HJ , Bril V . Advances and ongoing research in the treatment of autoimmune neuromuscular junction disorders. Lancet Neurol 2022; 21(3): e3

[97] Tian DS , Qin C , Dong MH , Heming M , Zhou LQ , Wang W , Cai SB , You YF , Shang K , Xiao J , Wang D , Li CR , Zhang M , Bu BT , Meyer zu Hörste G , Wang W . B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis. EMBO Mol Med 2024; 16(4): 966–987

[98] Oh S , Mao X , Manfredo-Vieira S , Lee J , Patel D , Choi EJ , Alvarado A , Cottman-Thomas E , Maseda D , Tsao PY , Ellebrecht CT , Khella SL , Richman DP , O’Connor KC , Herzberg U , Binder GK , Milone MC , Basu S , Payne AS . Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat Biotechnol 2023; 41(9): 1229–1238

[99] Granit V , Benatar M , Kurtoglu M , Miljković MD , Chahin N , Sahagian G , Feinberg MH , Slansky A , Vu T , Jewell CM , Singer MS , Kalayoglu MV , Howard JF Jr , Mozaffar T , Granit V , Benatar M , Mozaffar T , Chahin N , Howard JF Jr , Slansky AD , Feinberg MH , Sahagian G , Vu T , Pereira D , Steele J , Paredes ME , Benjamin C , Komanduri K , Habib AA , Fong JK , De La Cruz L , Dimitrova D , Chopra M , Holley K , DeMaria G , Tenorio A , Requena N , Brooks BM , Suresh N , Farias J , Miljković MD , Kurtoglu M , Ngo Casi M , Chowdhury A , Kamboh H , Stewart CA , Tosun M , Shan Y , Daniel S , Duvernay MT , Kireeva M , English E , Jewell CM , Singer MS , Kalayoglu MV . 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. Lancet Neurol 2023; 22(7): 578–590

[100] Allenbach Y , Mammen AL , Benveniste O , Stenzel W , Allenbach Y , Amato A , Aussey A , Benveniste O , De Bleecker J , de Groot I , de Visser M , Goebel H , Hervier B , Fischer N , Hilton-Jones D , Lamb J , Lundberg I , Mammen A , Mozaffar T , Nishino I , Pestronk A , Schara U , Stenzelr W . 224th ENMC International Workshop: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14–16 October 2016. Neuromuscul Disord 2018; 28(1): 87–99

[101] Anquetil C , Boyer O , Wesner N , Benveniste O , Allenbach Y . Myositis-specific autoantibodies, a cornerstone in immune-mediated necrotizing myopathy. Autoimmun Rev 2019; 18(3): 223–230

[102] Tiniakou E , Mammen AL . Idiopathic inflammatory myopathies and autoantibodies. Clin Rev Allergy Immunol 2017; 52(1): 59–70

[103] Qin C , Dong MH , Zhou LQ , Wang W , Cai SB , You YF , Shang K , Xiao J , Wang D , Li CR , Zhang M , Bu BT , Tian DS , Wang W . Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy. Proc Natl Acad Sci USA 2024; 121(6): e2315990121

[104] Volkov J , Nunez D , Mozaffar T , Stadanlick J , Werner M , Vorndran Z , Ellis A , Williams J , Cicarelli J , Lam Q , Furmanak T , Schmitt C , Hadi-Nezhad F , Thompson D , Miller C , Little C , Chang D , Basu S . Case study of CD19 CAR T therapy in a subject with immune-mediate necrotizing myopathy treated in the RESET-Myositis phase I/II trial. Mol Ther 2024; 32(11): 3821–3828

[105] Taubmann J , Müller F , Yalcin Mutlu M , Völkl S , Aigner M , Bozec A , Mackensen A , Grieshaber-Bouyer R , Schett G . CD19 chimeric antigen receptor T cell treatment: unraveling the role of B cells in systemic lupus erythematosus. Arthritis Rheumatol 2024; 76(4): 497–504

[106] Guffroy A , Jacquel L , Guffroy B , Martin T . CAR-T cells for treating systemic lupus erythematosus: a promising emerging therapy. Joint Bone Spine 2024; 91(5): 105702

[107] Anquetil C , Boyer O , Wesner N , Benveniste O , Allenbach Y . Myositis-specific autoantibodies, a cornerstone in immune-mediated necrotizing myopathy. Autoimmun Rev 2019; 18(3): 223–230

[108] Li YR , Lyu Z , Chen Y , Fang Y , Yang L . Frontiers in CAR-T cell therapy for autoimmune diseases. Trends Pharmacol Sci 2024; 45(9): 839–857

[109] Viaud S , Ma JSY , Hardy IR , Hampton EN , Benish B , Sherwood L , Nunez V , Ackerman CJ , Khialeeva E , Weglarz M , Lee SC , Woods AK , Young TS . Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory. Proc Natl Acad Sci USA 2018; 115(46): E10898–E10906

[110] Park HB , Kim KH , Kim JH , Kim SI , Oh YM , Kang M , Lee S , Hwang S , Lee H , Lee T , Park S , Lee JE , Jeong GR , Lee DH , Youn H , Choi EY , Son WC , Chung SJ , Chung J , Choi K . Improved safety of chimeric antigen receptor T cells indirectly targeting antigens via switchable adapters. Nat Commun. 2024; 15(1): 9917

[111] Chang PS , Chen YC , Hua WK , Hsu JC , Tsai JC , Huang YW , Kao YH , Wu PH , Wang PN , Chang YF , Chang MC , Chang YC , Jian SL , Lai JS , Lai MT , Yang WC , Shen CN , Wen KK , Wu SC . Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system. PLoS One 2024; 19(8): e0309245

[112] Ercilla-Rodríguez P , Sánchez-Díez M , Alegría-Aravena N , Quiroz-Troncoso J , Gavira-O'Neill CE , González-Martos R , Ramírez-Castillejo C . CAR-T lymphocyte-based cell therapies; mechanistic substantiation, applications and biosafety enhancement with suicide genes: new opportunities to melt side effects. Front Immunol 2024; 15: 1333150

[113] Meister H , Look T , Roth P , Pascolo S , Sahin U , Lee S , Hale BD , Snijder B , Regli L , Ravi VM , Heiland DH , Sentman CL , Weller M , Weiss T . Multifunctional mRNA-based CAR T cells display promising antitumor activity against glioblastoma. Clin Cancer Res 2022; 28(21): 4747–4756

[114] Fiorenza S , Ritchie DS , Ramsey SD , Turtle CJ , Roth JA . Value and affordability of CAR T-cell therapy in the United States. Bone Marrow Transplant 2020; 55(9): 1706–1715

[115] Lyman GH , Nguyen A , Snyder S , Gitlin M , Chung KC . Economic evaluation of chimeric antigen receptor T-cell therapy by site of care among patients with relapsed or refractory large B-cell lymphoma. JAMA Netw Open 2020; 3(4): e208117

[116] Ghilardi G , Fraietta JA , Gerson JN , Van Deerlin VM , Morrissette JJD , Caponetti GC , Paruzzo L , Harris JC , Chong EA , Susanibar Adaniya SP , Svoboda J , Nasta SD , Ugwuanyi OH , Landsburg DJ , Fardella E , Waxman AJ , Chong ER , Patel V , Pajarillo R , Kulikovskaya I , Lieberman DB , Cohen AD , Levine BL , Stadtmauer EA , Frey NV , Vogl DT , Hexner EO , Barta SK , Porter DL , Garfall AL , Schuster SJ , June CH , Ruella M . T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy. Nat Med 2024; 30(4): 984–989

[117] Di Blasi R , Le Gouill S , Bachy E , Cartron G , Beauvais D , Le Bras F , Gros FX , Choquet S , Bories P , Feugier P , Casasnovas O , Bay JO , Mohty M , Joris M , Gastinne T , Sesques P , Tudesq JJ , Vercellino L , Morschhauser F , Gat E , Broussais F , Houot R , Thieblemont C . Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis. Blood 2022; 140(24): 2584–2593

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