Application and Challenges of Chimeric Antigen Receptor T Cell Therapy in Systemic Rheumatic Diseases and Autoimmune Disorders

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy, originally developed for hematologic malignancies, has emerged as a transformative candidate for systemic rheumatic diseases and autoimmune disorders (AIDs). Its unique efficacy in refractory AIDs relies on depleting autoreactive B cells and driving antigen-naïve immune reconstitution, achieving durable drug-free remission in early-phase trials. Despite promising clinical and serological responses lasting 2–5 years without long-term immunosuppression, the field faces unmet needs: complex manufacturing, limited tissue penetration, antigen escape, immunological sequelae, and lack of predictive biomarkers. Existing reviews predominantly focus on oncology adaptations or isolated technical aspects, lacking systematic integration of mechanisms, challenges, and precision-oriented innovations for rheumatic diseases. This review comprehensively summarizes CAR-T's action mechanisms in AIDs, analyzes core clinical challenges, and highlights emerging strategies—including universal/in vivo-generated CAR-T cells, multitargeted/logic-gated designs, organ-homing engineering, and rational combinations with tolerance-enhancing agents. It further emphasizes multiomics integration (single-cell transcriptomics, spatial mapping, B-cell receptor/T-cell receptor repertoire analysis) for patient stratification and relapse prediction. By bridging mechanism-driven engineering with clinical translation, this work provides an actionable framework to advance CAR-T toward functional immune reset, enabling precision immunotherapy for refractory rheumatic diseases and AIDs.

Keywords

autoimmune disorders (AIDs) / biomarker discovery / CAR-T cell therapy / immune reconstitution / in vivo CAR-T / multiomics integration / precision immunology / universal CAR-T

References

[1] F. Porsch and C. J. Binder, “Autoimmune Diseases and Atherosclerotic Cardiovascular Disease,” Nature Reviews Cardiology 21, no. 11 (2024): 780–807.

[2] N. Conrad, S. Misra, J. Y. Verbakel, et al., “Incidence, Prevalence, and Co-Occurrence of Autoimmune Disorders Over Time and by Age, Sex, and Socioeconomic Status: A Population-Based Cohort Study of 22 Million Individuals in the UK,” Lancet 401, no. 10391 (2023): 1878–1890.

[3] L. Zeng, K. Yang, Q. He, et al., “Efficacy and Safety of Gut Microbiota-Based Therapies in Autoimmune and Rheumatic Diseases: A Systematic Review and Meta-Analysis of 80 Randomized Controlled Trials,” BMC Medicine [Electronic Resource] 22, no. 1 (2024): 110.

[4] G. Wigerblad and M. J. Kaplan, “Neutrophil Extracellular Traps in Systemic Autoimmune and Autoinflammatory Diseases,” Nature Reviews Immunology 23, no. 5 (2023): 274–288.

[5] U. Blache, S. Tretbar, U. Koehl, D. Mougiakakos, and S. Fricke, “CAR T Cells for Treating Autoimmune Diseases,” RMD Open 9, no. 4 (2023): e002907.

[6] W. A. Shaheen, M. N. Quraishi, and T. H. Iqbal, “Gut Microbiome and Autoimmune Disorders,” Clinical and Experimental Immunology 209, no. 2 (2022): 161–174.

[7] S. Mu, W. Wang, Q. Liu, et al., “Autoimmune Disease: A View of Epigenetics and Therapeutic Targeting,” Frontiers in Immunology 15 (2024): 1482728.

[8] J. A. Snowden, I. Sánchez-Ortega, S. Corbacioglu, et al., “Indications for Haematopoietic Cell Transplantation for Haematological Diseases, Solid Tumours and Immune Disorders: Current Practice in Europe, 2022,” Bone Marrow Transplantation 57, no. 8 (2022): 1217–1239.

[9] F. Del Galdo, A. Lescoat, P. G. Conaghan, et al., “EULAR Recommendations for the Treatment of Systemic Sclerosis: 2023 Update,” Annals of the Rheumatic Diseases 84, no. 1 (2025): 29–40.

[10] A. Mitra, A. Barua, L. Huang, S. Ganguly, Q. Feng, and B. He, “From Bench to Bedside: The History and Progress of CAR T Cell Therapy,” Frontiers in Immunology 14 (2023): 1188049.

[11] K. M. Cappell and J. N. Kochenderfer, “Long-Term Outcomes Following CAR T Cell Therapy: What We Know so Far,” Nature reviews Clinical Oncology 20, no. 6 (2023): 359–371.

[12] J. N. Brudno, M. V. Maus, and C. S. Hinrichs, “CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review,” Jama 332, no. 22 (2024): 1924–1935.

[13] J. N. Brudno and J. N. Kochenderfer, “Current Understanding and Management of CAR T Cell-Associated Toxicities,” Nature Reviews Clinical Oncology 21, no. 7 (2024): 501–521.

[14] R. Ohno and A. Nakamura, “Advancing Autoimmune Rheumatic Disease Treatment: CAR-T Cell Therapies—Evidence, Safety, and Future Directions,” Seminars in Arthritis and Rheumatism 67 (2024): 152479.

[15] D. J. Baker, Z. Arany, J. A. Baur, J. A. Epstein, and C. H. June, “CAR T Therapy Beyond Cancer: The Evolution of a Living Drug,” Nature 619, no. 7971 (2023): 707–715.

[16] Y. R. Li, Z. Lyu, Y. Chen, Y. Fang, and L. Yang, “Frontiers in CAR-T Cell Therapy for Autoimmune Diseases,” Trends in Pharmacological Sciences 45, no. 9 (2024): 839–857.

[17] X. Lyu, L. Gupta, E. Tholouli, and H. Chinoy, “Chimeric Antigen Receptor T Cell Therapy: A New Emerging Landscape in Autoimmune Rheumatic Diseases,” Rheumatology 63, no. 5 (2024): 1206–1216.

[18] D. S. Pisetsky, “Pathogenesis of Autoimmune Disease,” Nature Reviews Nephrology 19, no. 8 (2023): 509–524.

[19] K. Bieber, J. E. Hundt, X. Yu, et al., “Autoimmune Pre-Disease,” Autoimmunity Reviews 22, no. 2 (2023): 103236.

[20] S. L. Coss, D. Zhou, G. T. Chua, et al., “The Complement System and human Autoimmune Diseases,” Journal of Autoimmunity 137 (2023): 102979.

[21] H. Yuuki, T. Itamiya, Y. Nagafuchi, M. Ota, and K. Fujio, “B Cell Receptor Repertoire Abnormalities in Autoimmune Disease,” Frontiers in Immunology 15 (2024): 1326823.

[22] M. Dominguez-Villar and D. A. Hafler, “Regulatory T Cells in Autoimmune Disease,” Nature Immunology 19, no. 7 (2018): 665–673.

[23] P. J. Eggenhuizen, B. H. Ng, and J. D. Ooi, “Treg Enhancing Therapies to Treat Autoimmune Diseases,” International Journal of Molecular Sciences 21, no. 19 (2020): 7015.

[24] S. Sakaguchi, N. Mikami, J. B. Wing, A. Tanaka, K. Ichiyama, and N. Ohkura, “Regulatory T Cells and Human Disease,” Annual Review of Immunology 38 (2020): 541–566.

[25] Y. Xiang, M. Zhang, D. Jiang, Q. Su, and J. Shi, “The Role of Inflammation in Autoimmune Disease: A Therapeutic Target,” Frontiers in Immunology 14 (2023): 1267091.

[26] G. Schett, G. Nagy, G. Krönke, and D. Mielenz, “B-Cell Depletion in Autoimmune Diseases,” Annals of the Rheumatic Diseases 83, no. 11 (2024): 1409–1420.

[27] K. Shah, M. Leandro, M. Cragg, et al., “Disrupting B and T-Cell Collaboration in Autoimmune Disease: T-Cell Engagers Versus CAR T-Cell Therapy?,” Clinical and Experimental Immunology 217, no. 1 (2024): 15–30.

[28] B. H. Rovin, R. Furie, K. Latinis, et al., “Efficacy and Safety of rituximab in Patients With Active Proliferative Lupus Nephritis: The Lupus Nephritis Assessment With Rituximab Study,” Arthritis and Rheumatism 64, no. 4 (2012): 1215–1226.

[29] A. Mostkowska, G. Rousseau, and N. J. Raynal, “Repurposing of rituximab Biosimilars to Treat B Cell Mediated Autoimmune Diseases,” Faseb Journal 38, no. 5 (2024): e23536.

[30] T. G. Forsthuber, D. M. Cimbora, J. N. Ratchford, E. Katz, and O. Stüve, “B Cell-Based Therapies in CNS Autoimmunity: Differentiating CD19 and CD20 as Therapeutic Targets,” Therapeutic Advances in Neurological Disorders 11 (2018): 1756286418761697.

[31] X. Ye, Y. Zhao, W. Ma, et al., “The Potential of CD38 Protein as a Target for Autoimmune Diseases,” Autoimmunity Reviews 22, no. 4 (2023): 103289.

[32] L. Zeng, K. Yang, Y. Wu, et al., “Telitacicept: A Novel Horizon in Targeting Autoimmunity and Rheumatic Diseases,” Journal of Autoimmunity 148 (2024): 103291.

[33] H. Zhu, H. Q. Hu, H. L. Wei, et al., “Efficacy and Safety of telitacicept in Patients With lupus Nephritis,” Experimental and Therapeutic Medicine 28, no. 4 (2024): 371.

[34] J. L. Barnas, R. J. Looney, and J. H. Anolik, “B Cell Targeted Therapies in Autoimmune Disease,” Current Opinion in Immunology 61 (2019): 92–99.

[35] J. J. Sabatino,, A. K. Pröbstel, and S. S. Zamvil, “B Cells in Autoimmune and Neurodegenerative central Nervous System Diseases,” Nature Reviews Neuroscience 20, no. 12 (2019): 728–745.

[36] I. Abeles, C. Palma, N. Meednu, A. S. Payne, R. J. Looney, and J. H. Anolik, “B Cell-Directed Therapy in Autoimmunity,” Annual Review of Immunology 42, no. 1 (2024): 103–126.

[37] Q. Wang, D. Feng, S. Jia, Q. Lu, and M. Zhao, “B-Cell Receptor Repertoire: Recent Advances in Autoimmune Diseases,” Clinical Reviews in Allergy & Immunology 66, no. 1 (2024): 76–98.

[38] Z. L. Chang and Y. Y. Chen, “CARs: Synthetic Immunoreceptors for Cancer Therapy and beyond,” Trends in Molecular Medicine 23, no. 5 (2017): 430–450.

[39] Z. Eshhar, T. Waks, G. Gross, and D. G. Schindler, “Specific Activation and Targeting of Cytotoxic Lymphocytes Through Chimeric Single Chains Consisting of Antibody-Binding Domains and the Gamma or Zeta Subunits of the Immunoglobulin and T-Cell Receptors,” Proceedings of the National Academy of Sciences of the United States of America 90, no. 2 (1993): 720–724.

[40] H. M. Finney, A. D. Lawson, C. R. Bebbington, and A. N. Weir, “Chimeric Receptors Providing both Primary and Costimulatory Signaling in T Cells From a Single Gene Product,” Journal of Immunology 161, no. 6 (1998): 2791–2797.

[41] S. J. van der Stegen, M. Hamieh, and M. Sadelain, “The Pharmacology of Second-Generation Chimeric Antigen Receptors,” Nature Reviews Drug Discovery 14, no. 7 (2015): 499–509.

[42] N. Tokarew, J. Ogonek, S. Endres, M. von Bergwelt-Baildon, and S. Kobold, “Teaching an Old Dog New Tricks: Next-Generation CAR T Cells,” British Journal of Cancer 120, no. 1 (2019): 26–37.

[43] Y. Kagoya, S. Tanaka, T. Guo, et al., “A Novel Chimeric Antigen Receptor Containing a JAK-STAT Signaling Domain Mediates Superior Antitumor Effects,” Nature Medicine 24, no. 3 (2018): 352–359.

[44] M. S. Choudhery, T. Arif, R. Mahmood, and D. T. Harris, “CAR-T-Cell-Based Cancer Immunotherapies: Potentials, Limitations, and Future Prospects,” Journal of Clinical Medicine 13, no. 11 (2024): 3202.

[45] L. R. Neal, S. R. Bailey, M. M. Wyatt, et al., “The Basics of Artificial Antigen Presenting Cells in T Cell-Based Cancer Immunotherapies,” Journal of Immunology Research 2, no. 1 (2017): 68–79.

[46] S. A. Grupp, M. Kalos, D. Barrett, et al., “Chimeric Antigen Receptor-modified T Cells for Acute Lymphoid Leukemia,” New England Journal of Medicine 368, no. 16 (2013): 1509–1518.

[47] C. J. Bashor, I. B. Hilton, H. Bandukwala, D. M. Smith, and O. Veiseh, “Engineering the Next Generation of Cell-Based Therapeutics,” Nature Reviews Drug Discovery 21, no. 9 (2022): 655–675.

[48] R. C. Larson and M. V. Maus, “Recent Advances and Discoveries in the Mechanisms and Functions of CAR T Cells,” Nature Reviews Cancer 21, no. 3 (2021): 145–161.

[49] M. H. Haddadi, E. Hajizadeh-Saffar, M. Khosravi-Maharlooei, M. Basiri, B. Negahdari, and H. Baharvand, “Autoimmunity as a Target for Chimeric Immune Receptor Therapy: A New Vision to Therapeutic Potential,” Blood Reviews 41 (2020): 100645.

[50] M. Arjomandnejad, A. L. Kopec, and A. M. Keeler, “CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications,” Biomedicines 10, no. 2 (2022): 287.

[51] F. R. Kahmini and S. Shahgaldi, “Harnessing the Inherent Power of Chimeric Antigen Receptor (CAR)-Expressing Regulatory T Cells (CAR-Tregs) to Treat Autoimmune-Related Disorders,” Molecular Biology Reports 49, no. 5 (2022): 4069–4078.

[52] N. Adabi, S. Pordel, M. A. Rezaee, F. S. Shobeiri, and S. S. Shobeiri, “Application of CAR-T Cell Technology in Autoimmune Diseases and Human Immunodeficiency Virus Infection Treatment,” The Journal of Gene Medicine 25, no. 5 (2023): e3484.

[53] M. T. Mazzi, K. L. Hajdu, P. R. Ribeiro, and M. H. Bonamino, “CAR-T Cells Leave the Comfort Zone: Current and Future Applications Beyond Cancer,” Immunotherapy Advances 1, no. 1 (2020): ltaa006.

[54] T. Riet and M. Chmielewski, “Regulatory CAR-T Cells in Autoimmune Diseases: Progress and Current Challenges,” Frontiers in Immunology 13 (2022): 934343.

[55] B. Caël, E. Bôle-Richard, F. Garnache-Ottou, and F. Aubin, “CAR-T Cell Therapy: Recent Updates and Challenges in Autoimmune Diseases,” Journal of Allergy and Clinical Immunology (2024), S0091-6749(24)02354-6.

[56] L. Zeng, Y. Li, W. Xiang, W. Xiao, Z. Long, and L. Sun, “Advances in Chimeric Antigen Receptor T Cell Therapy for Autoimmune and Autoinflammatory Diseases and Their Complications,” Journal of Autoimmunity 150 (2024): 103350.

[57] J. Liu, Y. Zhao, and H. Zhao, “Chimeric Antigen Receptor T-Cell Therapy in Autoimmune Diseases,” Frontiers in Immunology 15 (2024): 1492552.

[58] A. R. Daamen and P. E. Lipsky, “Potential and Pitfalls of Repurposing the CAR-T Cell Regimen for the Treatment of Autoimmune Disease,” Annals of the Rheumatic Diseases 83, no. 6 (2024): 696–699.

[59] R. Kansal, N. Richardson, I. Neeli, et al., “Sustained B Cell Depletion by CD19-Targeted CAR T Cells Is a Highly Effective Treatment for Murine Lupus,” Science Translational Medicine 11, no. 482 (2019): eaav1648.

[60] K. B. Whittington, A. Prislovsky, J. Beaty, L. Albritton, M. Radic, and E. F. Rosloniec, “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,” Journal of Immunology 208, no. 1 (2022): 16–26.

[61] S. Kretschmann, S. Völkl, H. Reimann, et al., “Successful Generation of CD19 Chimeric Antigen Receptor T Cells From Patients With Advanced Systemic Lupus Erythematosus,” Transplantation and Cellular Therapy 29, no. 1 (2023): 27–33.

[62] A. Hoi, T. Igel, C. C. Mok, and L. Arnaud, “Systemic lupus erythematosus,” Lancet 403, no. 10441 (2024): 2326–2338.

[63] C. H. Siegel and L. R. Sammaritano, “Systemic Lupus Erythematosus: A Review,” Jama 331, no. 17 (2024): 1480–1491.

[64] T. Krickau, N. Naumann-Bartsch, M. Aigner, et al., “CAR T-Cell Therapy Rescues Adolescent With Rapidly Progressive Lupus Nephritis From Haemodialysis,” Lancet 403, no. 10437 (2024): 1627–1630.

[65] A. Mackensen, F. Müller, D. Mougiakakos, et al., “Anti-CD19 CAR T Cell Therapy for Refractory Systemic Lupus Erythematosus,” Nature Medicine 28, no. 10 (2022): 2124–2132.

[66] F. Müller, J. Taubmann, L. Bucci, et al., “CD19 CAR T-Cell Therapy in Autoimmune Disease—A Case Series With Follow-up,” New England Journal of Medicine 390, no. 8 (2024): 687–700.

[67] A. Aggarwal, T. A. P. Fernandes, A. Migowa, et al., “Childhood-Onset Systemic Lupus Erythematosus (cSLE): An International Perspective,” Current Allergy and Asthma Reports 24, no. 10 (2024): 559–569.

[68] F. De Benedetti, F. Diomedi Camassei, and F. Locatelli, “CAR T-Cell Therapy in Autoimmune Disease,” New England Journal of Medicine 390, no. 17 (2024): 1629.

[69] J. Shu, W. Xie, C. Mei, et al., “Safety and Clinical Efficacy of Relmacabtagene autoleucel (Relma-cel) for Systemic Lupus Erythematosus: A Phase 1 Open-Label Clinical Trial,” EClinicalMedicine 83 (2025): 103229.

[70] https://library.ehaweb.org/eha/2025/eha2025-congress/4161220/jingjing.feng.first-in-human.study.of.cd19.bcma.dual-targeting.fastcar-t.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D2%2Asearch%3DGC012F.

[71] E. Morand, R. Kandane-Rathnayake, J. Cortés-Hernández, et al., “OP0079-Clinical, Cellular Kinetics, Pharmacodynamics and Biomarker Data Up to 12 Months After YTB323 (Rapcabtagene Autoleucel), a Rapidly Manufactured CD19 CAR-T Therapy, From an Open-Label, Phase 1/2 Study in Severe Refractory SLE,” Annals of the Rheumatic Diseases 84 (2025): 68–70.

[72] C. Wu, Y. Fu, J. Liu, et al., “OP0074 Preliminary Results of CD19/BCMA Dual-Targeting FasTCAR-T Cells GC012F (AZD0120) in patients with refractory Systemic Lupus Erythematosus-an open-Label, single-arm Study,” Annals of the Rheumatic Diseases 84 (2025): 65.

[73] S. Sheikh, V. Derebail, N. Grover, et al., “OP0202 RESET-SLE: Clinical Trial Evaluating Rese-Cel (Resecabtagene Autoleucel), A Fully Human, Autologous 4-1BB Anti-CD19 CAR T Cell Therapy In Non-Renal Sle And Lupus Nephritis,” Annals of the Rheumatic Diseases 84 (2025): 168.

[74] N. M. Pietras, N. Gupta, A. A. Justiz Vaillant, and A. L. Pearson-Shaver, “Immune Thrombocytopenia,” in StatPearls, May 5, (StatPearls Publishing, 2024).

[75] M. Li, Y. Zhang, N. Jiang, et al., “Anti-CD19 CAR T Cells in Refractory Immune Thrombocytopenia of SLE,” New England Journal of Medicine 391, no. 4 (2024): 376–378.

[76] W. Wang, S. He, W. Zhang, et al., “BCMA-CD19 Compound CAR T Cells for Systemic Lupus Erythematosus: A Phase 1 Open-Label Clinical Trial,” Annals of the Rheumatic Diseases 83, no. 10 (2024): 1304–1314.

[77] Z. Hu, S. Cai, Y. Yu, et al., “BCMA-targeted CAR T Cell Therapy Can Effectively Induce Disease Remission in Refractory Lupus Nephritis,” Annals of the Rheumatic Diseases (2025), S0003-4967(25)04186-X.

[78] https://www.abelzeta.com/wp-content/uploads/2025/06/168-Toronto-lupus-congress-slides_20250522.pdf.

[79] X. He, F. Liu, M. Lu, C. Qian, and J. Mao, “Chimeric Antigen Receptor T-Cell Therapy in Pediatric Refractory Systemic Lupus Erythematosus,” The Innovation Medicine 3 (2025): 100119.

[80] C. Yang, C. Sun, B. Tan, et al., “Allogeneic Anti-CD19 CAR-T Cells Induce Remission in Refractory Systemic Lupus Erythematosus,” Cell Research 35, no. 8 (2025): 607–609.

[81] X. Wang, Y. Zhang, H. Wang, et al., “Allogeneic CD19-Targeting T Cells for Treatment-Refractory Systemic Lupus Erythematosus: A Phase 1 Trial,” Nature Medicine 31, no. 11 (2025): 3713–3724.

[82] J. Gao, M. Li, M. Sun, et al., “Efficacy and Safety of Allogeneic CD19 CAR NK-Cell Therapy in Systemic Lupus Erythematosus: A Case Series in China,” Lancet 406, no. 10522 (2026): 2968–2979.

[83] X. Wang, Y. Zhang, Y. Jin, et al., “An iPSC-Derived CD19/BCMA CAR-NK Therapy in a Patient With Systemic Sclerosis,” Cell 188, no. 16 (2025): 4225–4238.e12.

[84] Q. Wang, Z. X. Xiao, X. Zheng, et al., “In Vivo CD19 CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus,” New England Journal of Medicine 393, no. 15 (2025): 1542–1544.

[85] L. Cacciaguerra and E. P. Flanagan, “Updates in NMOSD and MOGAD Diagnosis and Treatment: A Tale of Two Central Nervous System Autoimmune Inflammatory Disorders,” Neurologic Clinics 42, no. 1 (2024): 77–114.

[86] A. Han, T. Peng, Y. Xie, et al., “Mitochondrial-Regulated Tregs: Potential Therapeutic Targets for Autoimmune Diseases of the Central Nervous System,” Frontiers in Immunology 14 (2023): 1301074.

[87] S. Rodríguez Murúa, M. F. Farez, and F. J. Quintana, “The Immune Response in Multiple Sclerosis,” Annual Review of Pathology 17 (2022): 121–139.

[88] G. Brittain, E. Roldan, T. Alexander, et al., “The Role of Chimeric Antigen Receptor T-Cell Therapy in Immune-Mediated Neurological Diseases,” Annals of Neurology 96, no. 3 (2024): 441–452.

[89] S. Arnett, S. H. Chew, U. Leitner, et al., “Sex Ratio and Age of Onset in AQP4 Antibody-Associated NMOSD: A Review and Meta-analysis,” Journal of Neurology 271, no. 8 (2024): 4794–4812.

[90] A. Uzawa, F. C. Oertel, M. Mori, F. Paul, and S. Kuwabara, “NMOSD and MOGAD: An Evolving Disease Spectrum,” Nature Reviews Neurology 20, no. 10 (2024): 602–619.

[91] C. Qin, D. S. Tian, L. Q. Zhou, et al., “Anti-BCMA CAR T-cell Therapy CT103A in Relapsed or Refractory AQP4-IgG Seropositive Neuromyelitis Optica Spectrum Disorders: Phase 1 Trial Interim Results,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 5.

[92] M. R. Tannemaat, M. G. Huijbers, and J. Verschuuren, “Myasthenia Gravis-Pathophysiology, Diagnosis, and Treatment,” Handbook of Clinical Neurology 200 (2024): 283–305.

[93] D. S. W. Lee, O. L. Rojas, and J. L. Gommerman, “B Cell Depletion Therapies in Autoimmune Disease: Advances and Mechanistic Insights,” Nature Reviews Drug Discovery 20, no. 3 (2021): 179–199.

[94] V. Granit, M. Benatar, M. Kurtoglu, et al., “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 Neurology 22, no. 7 (2023): 578–590.

[95] A. Haghikia, T. Hegelmaier, D. Wolleschak, et al., “Anti-CD19 CAR T Cells for Refractory Myasthenia Gravis,” Lancet Neurology 22, no. 12 (2023): 1104–1105.

[96] C. Qin, M. Zhang, D. P. Mou, et al., “Single-cell Analysis of Anti-BCMA CAR T Cell Therapy in Patients With central Nervous System Autoimmunity,” Science Immunology 9, no. 95 (2024): eadj9730.

[97] F. Fischbach, J. Richter, L. K. Pfeffer, et al., “CD19-Targeted Chimeric Antigen Receptor T Cell Therapy in Two Patients With Multiple Sclerosis,” Med 5, no. 6 (2024): 550–558.e2.

[98] C. Qin, M. H. Dong, L. Q. Zhou, et al., “Anti-BCMA CAR-T Therapy in Patients with Progressive Multiple Sclerosis,” Cell 188, no. 23 (2025): 6414–6423.e11.

[99] M. Caballero-Ávila, L. Martin-Aguilar, R. Collet-Vidiella, L. Querol, and E. Pascual-Goñi, “A Pathophysiological and Mechanistic Review of Chronic Inflammatory Demyelinating Polyradiculoneuropathy Therapy,” Frontiers in Immunology 16 (2025): 1575464.

[100] M. H. Dong, Z. C. Mei, L. Q. Zhou, et al., “Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Chronic Inflammatory Demyelinating Polyneuropathy,” Med 6, no. 9 (2025): 100704.

[101] L. Querol and M. C. Dalakas, “The Discovery of Autoimmune Nodopathies and the Impact of IgG4 Antibodies in Autoimmune Neurology,” Neurol Neuroimmunol Neuroinflamm 12, no. 1 (2025): e200365.

[102] C. B. Johnson, J. Fehmi, and S. Rinaldi, “The Immunology and Neuropathology of the Autoimmune Nodopathies,” Journal of Neuroimmunology 406 (2025): 578665.

[103] R. Collet-Vidiella, A. De Lorenzo, and L. Querol, “Autoimmune Nodopathies: Emerging Insights and Clinical Implications,” Current Opinion in Neurology 38, no. 5 (2025): 452–458.

[104] J. Motte, R. Klimas, M. Sgodzai, et al., “CD19-Targeted CAR T-cell Therapy for Treatment-Refractory Autoimmune Neuropathies,” Lancet Neurology 24, no. 7 (2025): 564–566.

[105] E. P. Flanagan, M. D. Geschwind, A. S. Lopez-Chiriboga, et al., “Autoimmune Encephalitis Misdiagnosis in Adults,” JAMA Neurology 80, no. 1 (2023): 30–39.

[106] J. Dalmau and F. Graus, “Diagnostic Criteria for Autoimmune Encephalitis: Utility and Pitfalls for Antibody-negative Disease,” Lancet Neurology 22, no. 6 (2023): 529–540.

[107] T. Hegelmaier, D. Wolleschak, V. Pappa, et al., “Chimeric Antigen Receptor T Cells in Treatment-Refractory DAGLA Antibody-Associated Encephalitis,” Med 6, no. 9 (2025): 100776.

[108] V. Liakouli, A. Ciancio, F. Del Galdo, R. Giacomelli, and F. Ciccia, “Systemic Sclerosis Interstitial Lung Disease: Unmet Needs and Potential Solutions,” Nature Reviews Rheumatology 20, no. 1 (2024): 21–32.

[109] C. Bergmann, F. Müller, J. H. W. Distler, et al., “Treatment of a Patient With Severe Systemic Sclerosis (SSc) Using CD19-Targeted CAR T Cells,” Annals of the Rheumatic Diseases 82, no. 8 (2023): 1117–1120.

[110] W. Merkt, M. Freitag, M. Claus, et al., “Third-Generation CD19.CAR-T Cell-Containing Combination Therapy in Scl70+ Systemic Sclerosis,” Annals of the Rheumatic Diseases 83, no. 4 (2024): 543–546.

[111] J. Auth, F. Müller, and S. Völkl, “CD19-Targeting CAR T-cell Therapy in Patients With Diffuse Systemic Sclerosis: A Case Series,” The Lancet Rheumatology (2024), S2665-9913(24)00282-0.

[112] X. Wang, X. Wu, B. Tan, et al., “Allogeneic CD19-Targeted CAR-T Therapy in Patients With Severe Myositis and Systemic Sclerosis,” Cell 187, no. 18 (2024): 4890–4904.e9.

[113] D. Khanna, M. Ghosh, A. Shah, et al., “OP0338 RESET-SScTM: Clinical Trial Evaluating Rese-Cel (Resecabtagene Autoleucel), A Fully Human, Autologous 4-1BB Anti-CD19 CAR T Cell Therapy In Systemic Sclerosis,” Annals of the Rheumatic Diseases 84 (2025): 275–276.

[114] D. Khanna, M. Wiesendanger, R. Nash, et al., “POS0656:Tolerability And Efficacy Of BMS-986353 (CC-97540), A CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy Manufactured Using A Next-Generation Process For Systemic Sclerosis: Updated Data From The Phase 1 Breakfree-1 Study,” Annals of the Rheumatic Diseases 84 (2025): 841–842.

[115] V. Sandhu, P. Fazeli, J. Medlin, et al., “OP0032:Treatment of Refractory Systemic Lupus Erythematosus With Off-the-Shelf iPSC-Derived Anti-CD19 CAR T-Cell Therapy,” Annals of the Rheumatic Diseases 84 (2025): 29–30.

[116] P. Patel, J. M. Marinock, A. Ajmeri, and L. H. Brent, “A Review of Antisynthetase Syndrome-Associated Interstitial Lung Disease,” International Journal of Molecular Sciences 25, no. 8 (2024): 4453.

[117] M. Alnoukari, O. G. De La Garza, K. Al Gburi, et al., “IVIG for Refractory Dysphagia in Antisynthetase Syndrome: A Truth Hard to Swallow,” Clinical Case Reports 10, no. 11 (2022): e6569.

[118] J. A. Huapaya, R. Hallowell, L. Silhan, et al., “Long-Term Treatment With Human Immunoglobulin for Antisynthetase Syndrome-Associated Interstitial Lung Disease,” Respiratory Medicine 154 (2019): 6–11.

[119] H. A. Qureshi, A. Bandhlish, R. P. DeConde, I. M. Humphreys, W. M. Abuzeid, and A. Jafari, “Initial Presentation of Granulomatosis With Polyangiitis as Progressive Skull Base Osteomyelitis,” Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties 84, no. 4 (2022): 342–346.

[120] V. Langlois, A. Gillibert, Y. Uzunhan, et al., “Rituximab and Cyclophosphamide in Antisynthetase Syndrome-Related Interstitial Lung Disease: An Observational Retrospective Study,” Journal of Rheumatology 47, no. 11 (2020): 1678–1686.

[121] A. C. Pecher, L. Hensen, R. Klein, et al., “CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome,” Jama 329, no. 24 (2023): 2154–2162.

[122] F. Müller, S. Boeltz, J. Knitza, et al., “CD19-Targeted CAR T Cells in Refractory Antisynthetase Syndrome,” Lancet 401, no. 10379 (2023): 815–818.

[123] J. Taubmann, J. Knitza, F. Müller, et al., “Rescue Therapy of Antisynthetase Syndrome With CD19-Targeted CAR-T Cells After Failure of Several B-Cell Depleting Antibodies,” Rheumatology 63, no. 1 (2024): e12–e14.

[124] A. París-Muñoz, R. M. Alcobendas-Rueda, C. Verdú-Sánchez, et al., “CD19 CAR-T Cell Therapy in a Pediatric Patient With MDA5+ Dermatomyositis and Rapidly Progressive Interstitial Lung Disease,” Med 6, no. 8 (2025): 100676.

[125] F. Müller, A. Wirsching, M. Hagen, et al., “BCMA CAR T Cells in a Patient With Relapsing Idiopathic Inflammatory Myositis After Initial and Repeat Therapy With CD19 CAR T Cells,” Nature Medicine 31, no. 6 (2025): 1793–1797.

[126] S. Oh and A. S. Payne, “Engineering Cell Therapies for Autoimmune Diseases: From Preclinical to Clinical Proof of Concept,” Immune Network 22, no. 5 (2022): e37.

[127] D. R. Fooksman, Z. Jing, and R. Park, “New Insights Into the Ontogeny, Diversity, Maturation and Survival of Long-Lived Plasma Cells,” Nature Reviews Immunology 24, no. 7 (2024): 461–470.

[128] M. Wang, V. M. DeStefano, L. Ding, et al., “Validation of BCMA-CD19 Compound CAR-T Therapy in SLE Overlap Syndrome: Over 1.5-Year Follow-Up,” Stem Cell Reviews and Reports 21, no. 6 (2025): 1750–1759.

[129] R. Nicolai, P. Merli, P. Moran Alvarez, et al., “Autologous CD19-Targeting CAR T Cells in a Patient With Refractory Juvenile Dermatomyositis,” Arthritis & Rheumatology 76, no. 10 (2024): 1560–1565.

[130] T. Mozaffar, E. Naddaf, N. Chahin, et al., “OP0316:RESET-MYOSITISTM: Clinical Trial Evaluating Rese-Cel (Resecabtagene Autoleucel), A Fully Human, Autologous 4-1BB Anti-CD19 CAR T Cell Therapy In Idiopathic Inflammatory Myopathies,” Annals of the Rheumatic Diseases 84 (2025): 254–255.

[131] M. Hagen, A. Wirsching, F. Müller, et al., “POS0062: Safety And Preliminary Efficacy of CD19 CAR T-Cell Treatment In Rheumatic Disease—Data From The Phase I/II Castle Basket Study,” Annals of the Rheumatic Diseases 84 (2025): 369–370.

[132] P. W. Cullinane, A. S. Carr, S. R. Irani, and T. T. Warner, “Stiff Person Syndrome,” Handbook of Clinical Neurology 203 (2024): 211–233.

[133] S. Bose and S. Jacob, “Stiff-Person Syndrome,” Practical Neurology 25, no. 1 (2025): 6–17.

[134] S. Faissner, J. Motte, M. Sgodzai, et al., “Successful Use of Anti-CD19 CAR T Cells in Severe Treatment-Refractory Stiff-Person Syndrome,” Proceedings of the National Academy of Sciences of the United States of America 121, no. 26 (2024): e2403227121.

[135] E. Schmidt, M. Kasperkiewicz, and P. Joly, “Pemphigus,” Lancet 394, no. 10201 (2019): 882–894.

[136] C. T. Ellebrecht, V. G. Bhoj, A. Nace, et al., “Reengineering Chimeric Antigen Receptor T Cells for Targeted Therapy of Autoimmune Disease,” Science 353, no. 6295 (2016): 179–184.

[137] C. Baldini, G. Fulvio, G. La Rocca, and F. Ferro, “Update on the Pathophysiology and Treatment of Primary Sjögren Syndrome,” Nature Reviews Rheumatology 20, no. 8 (2024): 473–491.

[138] S. De Vita and S. Gandolfo, “Predicting Lymphoma Development in Patients With Sjögren's Syndrome,” Expert Review of Clinical Immunology 15, no. 9 (2019): 929–938.

[139] M. Beydon, S. McCoy, Y. Nguyen, T. Sumida, X. Mariette, and R. Seror, “Epidemiology of Sjögren Syndrome,” Nature Reviews Rheumatology 20, no. 3 (2024): 158–169.

[140] V. Devauchelle-Pensec, X. Mariette, S. Jousse-Joulin, et al., “Treatment of Primary Sjögren Syndrome With rituximab: A Randomized Trial,” Annals of Internal Medicine 160, no. 4 (2014): 233–242.

[141] S. Brown, N. Navarro Coy, C. Pitzalis, et al., “The TRACTISS Protocol: A Randomised Double Blind Placebo Controlled Clinical Trial of Anti-B-Cell Therapy in Patients With Primary Sjögren's Syndrome,” BMC Musculoskeletal Disorders [Electronic Resource] 15 (2014): 21.

[142] L. Sheng, Y. Zhang, Q. Song, et al., “Concurrent Remission of Lymphoma and Sjögren's Disease Following Anti-CD19 Chimeric Antigen Receptor-T Cell Therapy for Diffuse Large B-Cell Lymphoma: A Case Report,” Frontiers in Immunology 14 (2023): 1298815.

[143] J. F. Ma, T. Xu, H. X. Zhu, et al., “Identification of Pathogenic PD-1+CD8+ T Cells for Effective Chimeric Antigen Receptor Therapy in a Murine Model of Sjögren Disease,” Arthritis & Rheumatology 77, no. 8 (2025): 1026–1040.

[144] A. Shimabukuro-Vornhagen, B. Böll, P. Schellongowski, et al., “Critical Care Management of Chimeric Antigen Receptor T-Cell Therapy Recipients,” CA: A Cancer Journal for Clinicians 72, no. 1 (2022): 78–93.

[145] B. Zhang, Y. Wang, Y. Yuan, et al., “In Vitro Elimination of Autoreactive B Cells From Rheumatoid Arthritis Patients by Universal Chimeric Antigen Receptor T Cells,” Annals of the Rheumatic Diseases 80, no. 2 (2021): 176–184.

[146] Y. Li, S. Li, X. Zhao, et al., “Fourth-Generation Chimeric Antigen Receptor T-Cell Therapy Is Tolerable and Efficacious in Treatment-Resistant Rheumatoid Arthritis,” Cell Research 35, no. 3 (2025): 220–223.

[147] A. Haghikia, T. Hegelmaier, D. Wolleschak, et al., “Clinical Efficacy and Autoantibody Seroconversion With CD19-CAR T Cell Therapy in a Patient With Rheumatoid Arthritis and Coexisting Myasthenia Gravis,” Annals of the Rheumatic Diseases 83, no. 11 (2024): 1597–1598.

[148] V. Mohammadi, A. J. Maleki, M. Nazari, et al., “Chimeric Antigen Receptor (CAR)-Based Cell Therapy for Type 1 Diabetes Mellitus (T1DM); Current Progress and Future Approaches,” Stem Cell Reviews and Reports 20, no. 3 (2024): 585–600.

[149] L. Zhang, T. Sosinowski, A. R. Cox, et al., “Chimeric Antigen Receptor (CAR) T Cells Targeting a Pathogenic MHC Class II:Peptide Complex Modulate the Progression of Autoimmune Diabetes,” Journal of Autoimmunity 96 (2019): 50–58.

[150] S. Kobayashi, M. A. Thelin, H. L. Parrish, et al., “A Biomimetic Five-Module Chimeric Antigen Receptor (5MCAR) Designed to Target and Eliminate Antigen-Specific T Cells,” Proceedings of the National Academy of Sciences of the United States of America 117, no. 46 (2020): 28950–28959.

[151] M. Lanzillotta, E. Culver, A. Sharma, et al., “Fibrotic Phenotype of IgG4-Related Disease,” The Lancet Rheumatology 6, no. 7 (2024): e469–e480.

[152] G. Katz, Y. Hernandez-Barco, D. Palumbo, T. V. Guy, L. Dong, and C. A. Perugino, “Proliferative Features of IgG4-Related Disease,” The Lancet Rheumatology 6, no. 7 (2024): e481–e492.

[153] Z. S. Wallace, G. Katz, Y. G. Hernandez-Barco, and M. C. Baker, “Current and Future Advances in Practice: IgG4-Related Disease,” Rheumatology Advances in Practice 8, no. 2 (2024): rkae020.

[154] Y. Sun, S. Huang, B. Zhang, et al., “Efficacy and Safety of anti-CD19 CAR-T in a Mouse Model of IgG4-Related Disease,” International Immunopharmacology 145 (2025): 113779.

[155] S. Cai, Y. Chen, C. Ye, et al., “Anti-BCMA CAR-T for Treatment of IgG4-Related Disease: Clinical Assessment and Single Cell Transcriptomic Analysis,” The Lancet Rheumatology 7 (2025): e834–e836.

[156] M. Yang, T. Liu, B. Chen, et al., “POS0061 BCMA-CD19 Dual-Targeting CAR-T Cell For The Treatment Of Refractory Thrombocytopenia Associated With Autoimmune Diseases,” Annals of the Rheumatic Diseases 84 (2025): 368–369.

[157] G. Trivioli, M. Casal Moura, A. Kronbichler, et al., “Advances in the Treatment of ANCA-Associated Vasculitis,” Nature Reviews Rheumatology 21, no. 7 (2025): 396–413.

[158] D. Jayne, “Emerging Targeted Therapies in ANCA-Associated Vasculitis,” Rheumatology 64, no. Supplement_1 (2025): i15–i18.

[159] I. Minopoulou, A. Wilhelm, F. N. Albach, et al., “OP0294:Targeted B-Cell Therapy by Anti-CD19 CAR T Cells Induces Stable Disease Remission In Treatment-Refractory Anca-Associated Vasculitis,” Annals of the Rheumatic Diseases 84 (2025): 2.

[160] A. Freuchet, A. Salama, S. Bézie, et al., “IL-34 Deficiency Impairs FOXP3+ Treg Function in a Model of Autoimmune Colitis and Decreases Immune Tolerance Homeostasis,” Clinical and Translational Medicine 12, no. 8 (2022): e988.

[161] S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, and M. Toda, “Immunologic Self-Tolerance Maintained by Activated T Cells Expressing IL-2 Receptor Alpha-Chains (CD25). Breakdown of a Single Mechanism of Self-Tolerance Causes Various Autoimmune Diseases,” Journal of Immunology 155, no. 3 (1995): 1151–1164.

[162] R. Zhang, J. Miao, and P. Zhu, “Regulatory T Cell Heterogeneity and Therapy in Autoimmune Diseases,” Autoimmunity Reviews 20, no. 5 (2021): 102715.

[163] C. Raffin, L. T. Vo, and J. A. Bluestone, “Treg Cell-Based Therapies: Challenges and Perspectives,” Nature Reviews Immunology 20, no. 3 (2020): 158–172.

[164] Y. Sun, Y. Yuan, B. Zhang, and X. Zhang, “CARs: A New Approach for the Treatment of Autoimmune Diseases,” Science China Life Sciences 66, no. 4 (2023): 711–728.

[165] G. Műzes and F. Sipos, “CAR-Based Therapy for Autoimmune Diseases: A Novel Powerful Option,” Cells 12, no. 11 (2023): 1534.

[166] W. H. Wu and D. F. Zegarra-Ruiz, “Diehl GE. Intestinal Microbes in Autoimmune and Inflammatory Disease,” Frontiers in Immunology 11 (2020): 597966.

[167] P. Desreumaux, A. Foussat, M. Allez, et al., “Safety and Efficacy of Antigen-Specific Regulatory T-Cell Therapy for Patients With Refractory Crohn's Disease,” Gastroenterology 143, no. 5 (2012): 1207–1217.e2.

[168] E. Elinav, T. Waks, and Z. Eshhar, “Redirection of Regulatory T Cells With Predetermined Specificity for the Treatment of Experimental Colitis in Mice,” Gastroenterology 134, no. 7 (2008): 2014–2024.

[169] D. Blat, E. Zigmond, Z. Alteber, T. Waks, and Z. Eshhar, “Suppression of Murine Colitis and Its Associated Cancer by Carcinoembryonic Antigen-Specific Regulatory T Cells,” Molecular Therapy 22, no. 5 (2014): 1018–1028.

[170] M. Pawlak, D. DeTomaso, A. Schnell, et al., “Induction of a Colitogenic Phenotype in Th1-Like Cells Depends on Interleukin-23 Receptor Signaling,” Immunity 55, no. 9 (2022): 1663–1679.e6.

[171] M. Fransson, J. Burman, C. Lindqvist, C. Atterby, J. Fagius, and A. Loskog, “T Regulatory Cells Lacking CD25 Are Increased in MS During Relapse,” Autoimmunity 43, no. 8 (2010): 590–597.

[172] M. Dominguez-Villar, C. M. Baecher-Allan, and D. A. Hafler, “Identification of T Helper Type 1-Like, Foxp3+ Regulatory T Cells in human Autoimmune Disease,” Nature Medicine 17, no. 6 (2011): 673–675.

[173] T. Sumida, M. R. Lincoln, C. M. Ukeje, et al., “Activated β-Catenin in Foxp3+ Regulatory T Cells Links Inflammatory Environments to Autoimmunity,” Nature Immunology 19, no. 12 (2018): 1391–1402.

[174] T. S. Sumida, N. T. Cheru, and D. A. Hafler, “The Regulation and Differentiation of Regulatory T Cells and Their Dysfunction in Autoimmune Diseases,” Nature Reviews Immunology 24, no. 7 (2024): 503–517.

[175] J. Derdelinckx, T. Reynders, I. Wens, N. Cools, and B. Willekens, “Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD,” International Journal of Molecular Sciences 22, no. 15 (2021): 7925.

[176] Y. Li, Y. Lu, S. H. Lin, et al., “Insulin Signaling Establishes a Developmental Trajectory of Adipose Regulatory T Cells,” Nature Immunology 22, no. 9 (2021): 1175–1185.

[177] M. Shahnawaz, P. Dar, S. I. Rafiqi, et al., “Antigen-Specific Chimeric Antigen Receptor-T Regulatory Cells Home to Human Islets, Suppress Cytotoxic T Lymphocytes and Reverse Type 1 Diabetes,” Diabetes Technol Ther (2025). Online ahead of print.

[178] A. Pierini, B. P. Iliopoulou, H. Peiris, et al., “T Cells Expressing Chimeric Antigen Receptor Promote Immune Tolerance,” JCI Insight 2, no. 20 (2017): e92865.

[179] T. Pieper, T. Riet, V. Saetzler, et al., “ENTPD3-Specific CAR Regulatory T Cells for Local Immune Control in T1D,” 2024.11.12.622951, eprint.

[180] P. S. Giri, M. Dwivedi, N. C. Laddha, R. Begum, and A. H. Bharti, “Altered Expression of Nuclear Factor of Activated T Cells, Forkhead Box P3, and Immune-Suppressive Genes in Regulatory T Cells of Generalized Vitiligo Patients,” Pigment Cell & Melanoma Research 33, no. 4 (2020): 566–578.

[181] D. S. Hegab and M. A. Attia, “Decreased Circulating T Regulatory Cells in Egyptian Patients With Nonsegmental Vitiligo: Correlation With Disease Activity,” Dermatology Research and Practice 2015 (2015): 145409.

[182] Z. Mukhatayev, E. R. Dellacecca, C. Cosgrove, et al., “Antigen Specificity Enhances Disease Control by Tregs in Vitiligo,” Frontiers in Immunology 11 (2020): 581433.

[183] G. P. Wright, C. A. Notley, S. A. Xue, et al., “Adoptive Therapy With Redirected Primary Regulatory T Cells Results in Antigen-Specific Suppression of Arthritis,” Proceedings of the National Academy of Sciences of the United States of America 106, no. 45 (2009): 19078–19083.

[184] M. Doglio, A. Ugolini, C. Bercher-Brayer, et al., “Regulatory T Cells Expressing CD19-Targeted Chimeric Antigen Receptor Restore Homeostasis in Systemic Lupus Erythematosus,” Nature Communications 15, no. 1 (2024): 2542.

[185] M. Norelli, B. Camisa, G. Barbiera, et al., “Monocyte-Derived IL-1 and IL-6 Are Differentially Required for Cytokine-Release Syndrome and Neurotoxicity due to CAR T Cells,” Nature Medicine 24, no. 6 (2018): 739–748.

[186] V. Staedtke, R. Y. Bai, K. Kim, et al., “Disruption of a Self-Amplifying Catecholamine Loop Reduces Cytokine Release Syndrome,” Nature 564, no. 7735 (2018): 273–277.

[187] F. Korell, M. L. Schubert, T. Sauer, et al., “Infection Complications After Lymphodepletion and Dosing of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or B Cell Non-Hodgkin Lymphoma,” Cancers (Basel) 13, no. 7 (2021): 1684.

[188] K. Rejeski, M. D. Jain, N. N. Shah, M. A. Perales, and M. Subklewe, “Immune Effector Cell-Associated Haematotoxicity After CAR T-Cell Therapy: From Mechanism to Management,” The Lancet Haematology 11, no. 6 (2024): e459–e470.

[189] M. P. Hamilton, T. Sugio, T. Noordenbos, et al., “Risk of Second Tumors and T-Cell Lymphoma After CAR T-Cell Therapy,” New England Journal of Medicine 390, no. 22 (2024): 2047–2060.

[190] FDA Requires Boxed Warning for T cell Malignancies Following Treatment With BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies. FDA Press Release. 18. 04. 2024.

[191] H. Lin, J. Cheng, W. Mu, J. Zhou, and L. Zhu, “Advances in Universal CAR-T Cell Therapy,” Frontiers in Immunology 12 (2021): 744823.

[192] G. Schett, F. Müller, J. Taubmann, et al., “Advancements and Challenges in CAR T Cell Therapy in Autoimmune Diseases,” Nature Reviews Rheumatology 20, no. 9 (2024): 531–544.

[193] A. M. Konitsioti, H. Prüss, S. Laurent, G. R. Fink, C. Heesen, and C. Warnke, “Chimeric Antigen Receptor T-Cell Therapy for Autoimmune Diseases of the central Nervous System: A Systematic Literature Review,” Journal of Neurology 271, no. 10 (2024): 6526–6542.

[194] C. R. Maldini, G. I. Ellis, and J. L. Riley, “CAR T Cells for Infection, Autoimmunity and Allotransplantation,” Nature Reviews Immunology 18, no. 10 (2018): 605–616.

[195] J. D. Isaacs, “CAR T Cells—A New Horizon for Autoimmunity?,” New England Journal of Medicine 390, no. 8 (2024): 758–759.

[196] A. C. Pecher, L. Hensen, R. Schairer-Marquardt, et al., “Relapse After Anti-CD19 CAR T-Cell Therapy in a Patient With Severe Rheumatoid Arthritis and Multiple Sclerosis Effectively Treated by Autologous Stem Cell Transplantation,” Annals of the Rheumatic Diseases 84, no. 7 (2025): 1284–1286.

[197] J. A. Fraietta, S. F. Lacey, E. J. Orlando, I. Pruteanu-Malinici, M. Gohil, and S. Lundh, “Determinants of Response and Resistance to CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy of Chronic Lymphocytic Leukemia,” Nature Medicine 24, no. 5 (2018): 563–571.

[198] D. Kasakovski, L. Xu, and Y. Li, “T Cell Senescence and CAR-T Cell Exhaustion in Hematological Malignancies,” Journal of Hematology & Oncology 11, no. 1 (2018): 91.

[199] B. D. Santomasso, J. H. Park, D. Salloum, et al., “Clinical and Biological Correlates of Neurotoxicity Associated With CAR T-Cell Therapy in Patients With B-Cell Acute Lymphoblastic Leukemia,” Cancer Discovery 8, no. 8 (2018): 958–971.

[200] H. Luo, N. Wang, L. Huang, et al., “Inflammatory Signatures for Quick Diagnosis of Life-Threatening Infection During the CAR T-Cell Therapy,” Journal for ImmunoTherapy of Cancer 7, no. 1 (2019): 271.

[201] M. Hagen, F. Müller, A. Wirsching, et al., “Local Immune Effector Cell-Associated Toxicity Syndrome in CAR T-Cell Treated Patients With Autoimmune Disease: An Observational Study,” The Lancet Rheumatology 7, no. 6 (2025): e424–e433.

[202] C. Wu, R. Wang, Y. Ye, S. Ye, and Q. Fu, “Local Immune Effector Cell-Associated Toxicity Syndrome in CAR T-Cell Treated Patients With Refractory Systemic Lupus Erythematosus,” The Lancet Rheumatology (2025), S2665-9913(25)00221-8.

[203] J. Frede, J. C. Poller, K. Shi, et al., “The Endogenous T Cell Landscape Is Reshaped by CAR-T Cell Therapy and Predicts Treatment Response in Multiple Myeloma,” Leukemia 39, no. 12 (2025): 3004–3014.

[204] J. Yang, Y. Chen, Y. Jing, M. R. Green, and L. Han, “Advancing CAR T Cell Therapy Through the Use of Multidimensional Omics Data,” Nature Reviews Clinical Oncology 20, no. 4 (2023): 211–228.

[205] Y. Cui, M. David, L. Bouchareychas, et al., “IL23R-Specific CAR Tregs for the Treatment of Crohn's Disease,” Journal of Crohn's and Colitis 19 (2024): jjae135.

[206] P. Henschel, S. Landwehr-Kenzel, N. Engels, et al., “Supraphysiological FOXP3 Expression in human CAR-Tregs Results in Improved Stability, Efficacy, and Safety of CAR-Treg Products for Clinical Application,” Journal of Autoimmunity 138 (2023): 103057.

[207] X. Huang, N. Kong, X. Zhang, Y. Cao, R. Langer, and W. Tao, “The Landscape of mRNA Nanomedicine,” Nature Medicine 28, no. 11 (2022): 2273–2287.

[208] E. Rohner, R. Yang, K. S. Foo, A. Goedel, and K. R. Chien, “Unlocking the Promise of mRNA Therapeutics,” Nature Biotechnology 40, no. 11 (2022): 1586–1600.

[209] R. Greco, T. Alexander, N. Del Papa, et al., “Innovative Cellular Therapies for Autoimmune Diseases: Expert-Based Position Statement and Clinical Practice Recommendations From the EBMT Practice Harmonization and Guidelines Committee,” EClinicalMedicine 69 (2024): 102476.

[210] T. L. Hunter, Y. Bao, Y. Zhang, et al., “In Vivo CAR T Cell Generation to Treat Cancer and Autoimmune Disease,” Science 388, no. 6753 (2025): 1311–1317.

[211] J. B. Chung, J. N. Brudno, D. Borie, and J. N. Kochenderfer, “Chimeric Antigen Receptor T Cell Therapy for Autoimmune Disease,” Nature Reviews Immunology 24, no. 11 (2024): 830–845.

[212] Y. R. Li, Y. Zhu, Y. Fang, Z. Lyu, and L. Yang, “Emerging Trends in Clinical Allogeneic CAR Cell Therapy,” Med 6, no. 8 (2025): 100677.

[213] A. Bot, A. Scharenberg, K. Friedman, et al., “In Vivo Chimeric Antigen Receptor (CAR)-T Cell Therapy,” Nature Reviews Drug Discovery 25, no. 2 (2026): 116–137.

[214] L. Zhang, Z. Gao, H. Pan, et al., “BCMA-Targeted T-Cell Engager for Autoimmune Hemolytic Anemia After CD19 CAR T-Cell Therapy,” New England Journal of Medicine 392, no. 22 (2025): 2282–2284.

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