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REVIEW PAPER
The role and potential of CD19-targeted chimeric antigen receptor T-cell therapy in systemic sclerosis
1
Department of Hematology, Institute of Medical Sciences, University of Opole, Poland
Submission date: 2025-12-28
Final revision date: 2026-05-23
Acceptance date: 2026-06-16
Publication date: 2026-07-10
Corresponding author
Krzysztof Michalak
Department of Hematology, Institute of Medical Sciences, University of Opole, 53 Kośnego St., 45-372 Opole, Poland
Department of Hematology, Institute of Medical Sciences, University of Opole, 53 Kośnego St., 45-372 Opole, Poland
Reumatologia 2026;64(4):322-331
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Systemic sclerosis (SSc) remains a challenge due to high mortality and resistance to treatment. Chimeric antigen receptor T-cell (CAR-T) technology (anti-CD19) may offer an opportunity for an immune system reset and long-term disease remission, eliminating the need for lifelong medication.
Material and Methods:
This narrative review is based on a literature search in the PubMed and Scopus databases from 2023 to 2026. The main search phrases were: “CAR-T in systemic sclerosis”, “CAR-T scleroderma”, and “CAR-T SSc.”
Results:
CD19-targeted CAR-T therapy led to significant clinical improvement across analyzed cases. The median modified Rodnan skin score decreased by 8–13 points within 3–6 months. Disease activity, measured by the European Scleroderma Trials and Research Group Activity Index (EUSTAR-AI), showed a mean improvement ranging from 2.1 to 4.2 points. Pulmonary function remained stable or improved, with forced vital capacity increasing by up to 7% in responders. The safety profile was manageable, primarily consisting of grade 1 cytokine release syndrome in approximately 75–80% of patients.
Conclusions:
CD19-targeted CAR-T therapy is a promising investigational option for patients with refractory SSc. Limitations include small study groups and a lack of randomized controlled trials, warranting further validation in ongoing clinical studies.
Systemic sclerosis (SSc) remains a challenge due to high mortality and resistance to treatment. Chimeric antigen receptor T-cell (CAR-T) technology (anti-CD19) may offer an opportunity for an immune system reset and long-term disease remission, eliminating the need for lifelong medication.
Material and Methods:
This narrative review is based on a literature search in the PubMed and Scopus databases from 2023 to 2026. The main search phrases were: “CAR-T in systemic sclerosis”, “CAR-T scleroderma”, and “CAR-T SSc.”
Results:
CD19-targeted CAR-T therapy led to significant clinical improvement across analyzed cases. The median modified Rodnan skin score decreased by 8–13 points within 3–6 months. Disease activity, measured by the European Scleroderma Trials and Research Group Activity Index (EUSTAR-AI), showed a mean improvement ranging from 2.1 to 4.2 points. Pulmonary function remained stable or improved, with forced vital capacity increasing by up to 7% in responders. The safety profile was manageable, primarily consisting of grade 1 cytokine release syndrome in approximately 75–80% of patients.
Conclusions:
CD19-targeted CAR-T therapy is a promising investigational option for patients with refractory SSc. Limitations include small study groups and a lack of randomized controlled trials, warranting further validation in ongoing clinical studies.
REFERENCES (36)
1.
Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease – A Case Series with Follow-up. N Engl J Med 2024; 390: 687–700, DOI: 10.1056/NEJMoa2308917.
2.
Chen L, Huang R, Huang C, et al. Cell therapy for scleroderma: progress in mesenchymal stem cells and CAR-T treatment. Front Med 2025; 11: 1530887, DOI: 10.3389/fmed.2024.1530887.
3.
Asano Y. The Pathogenesis of Systemic Sclerosis: An Understanding Based on a Common Pathologic Cascade across Multiple Organs and Additional Organ-Specific Pathologies. JCM 2020; 9: 2687, DOI: 10.3390/jcm9092687.
4.
Ramalingam S, Shah A. Stem Cell Therapy as a Treatment for Autoimmune Disease-Updates in Lupus, Scleroderma, and Multiple Sclerosis. Curr Allergy Asthma Rep 2021; 21: 22, DOI: 10.1007/s11882-021-00996-y.
5.
Cras A, Farge D, Carmoi T, et al. Update on mesenchymal stem cell-based therapy in lupus and scleroderma. Arthritis Res Ther 2015; 17: 301, DOI: 10.1186/s13075-015-0819-7.
6.
Hagen M, Wirsching A, Bohr D, et al. CAR T-cell therapy in rheumatology-What we know so far? Z Rheumatol 2024; 83: 485–491, DOI: 10.1007/s00393-024-01514-x [Article in German].
7.
Auth J, Müller F, Völkl S, et al. CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series. Lancet Rheumatol 2025; 7: e83–93, DOI: 10.1016/S2665-9913(24)00282-0.
8.
Wang X, Wu X, Tan B, et al. Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis. Cell 2024; 187: 4890–4904.e9, DOI: 10.1016/j.cell.2024. 06.027.
9.
Pecher A-C, Hensen L, Schairer R, et al. CD19-targeting CAR T cell therapy in five patients with systemic sclerosis unsuitable for autologous stem cell transplantation. EULAR Rheumatology Open 2025; S3050708125000084, DOI: 10.1016/j.ero.2025.03.005.
10.
Yoshizaki A, Fukasawa T, Ebata S, et al. Involvement of B cells in the development of systemic sclerosis. Front Immunol 2022; 13: 938785, DOI: 10.3389/fimmu.2022.938785.
11.
Claus M, Freitag M, Ewald M, et al. Immunological effects of CD19.CAR-T cell therapy in systemic sclerosis: an extended case study. Arthritis Res Ther 2024; 26: 211, DOI: 10.1186/s13075-024-03451-1.
12.
Garantziotis P, Auth J, Schett G, Bergmann C. CAR T-cell therapy in systemic sclerosis: the next frontier in immune modulation. Curr Opin Rheumatol 2026; 38: 60–68, DOI: 10.1097/BOR.0000000000001133.
13.
Zhao K, Kong C, Shi N, et al. Potential angiogenic, immunomodulatory, and antifibrotic effects of mesenchymal stem cell-derived extracellular vesicles in systemic sclerosis. Front Immunol 2023; 14: 1125257, DOI: 10.3389/fimmu.2023.1125257.
14.
Albach FN, Minopoulou I, Wilhelm A, et al. Targeting autoimmunity with CD19-CAR T-cell therapy: efficacy and seroconversion in diffuse systemic sclerosis and rheumatoid arthritis. Rheumatology 2025; 64: 4075–4077, DOI: 10.1093/rheumatology/keaf077.
15.
Müller F, Hagen M, Wirsching A, et al. CD19 CAR-T cells for treatment-refractory autoimmune diseases: the phase 1/2 CASTLE basket trial. Nat Med 2026; 32: 1142–1151, DOI: 10.1038/ s41591-025-04185-6.
16.
Bergmann C, Müller F, Distler JHW, et al. Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells. Ann Rheum Dis 2023; 82: 1117–20, DOI: 10.1136/ard-2023-223952.
17.
Berry CT, Frazee CS, Herman PJ, et al. Current advancements in cellular immunotherapy for autoimmune disease. Semin Immunopathol 2025; 47: 7, DOI: 10.1007/s00281-024-01034-5.
18.
Wu Y, Han L, Wang Y, et al. CAR-T therapy: pioneering a new era in the treatment of autoimmune diseases. Front Immunol 2025; 16: 1625166, DOI: 10.3389/fimmu.2025.1625166.
19.
Arvanitis P, Tziotis A, Papadimatos S, et al. Pathogenesis, Diagnosis, and Management of Cytokine Release Syndrome in Patients with Cancer: Focus on Infectious Disease Considerations. Curr Oncol 2025; 32: 198, DOI:10.3390/curroncol32040198.
20.
Sterner RC, Sterner RM. Immune effector cell associated neurotoxicity syndrome in chimeric antigen receptor-T cell therapy. Front Immunol 2022; 13: 879608, DOI: 10.3389/fimmu.2022. 879608.
21.
Wehrli M, Gallagher K, Chen YB, et al. Single-center experience using anakinra for steroid-refractory immune effector cell- associated neurotoxicity syndrome (ICANS). J Immunother Cancer 2022; 10: e003847, DOI: 10.1136/jitc-2021-003847.
22.
Sakkas LI, Katsiari C, Syrmou V, Chikanza IC. CAR-T cells in systemic sclerosis. Clin Rheumatol 2026; 45: 651–656, DOI: 10.1007/s10067-025-07554-1.
23.
Lee BW, Kwon EJ, Ju JH. Chimeric Antigen Receptor T-cell therapy in systemic autoimmune rheumatic diseases: current insights and future prospects. J Rheum Dis 2025; 32: 154–165, DOI: 10.4078/jrd.2024.0122.
24.
Bishop MR. Late complications and long-term care of adult CAR T-cell patients. Hematology Am Soc Hematol Educ Program 2024; 2024: 109–115, DOI: 10.1182/hematology.2024000534.
25.
Dahunsi D, Eleanya C, Akintunde A, et al. Prolonged Cytopenia with CAR-T Cell Therapy and Management Recommendations. Clin Hematol Int 2025; 7: 47–54, DOI: 10.46989/001c.126463.
26.
Testa U, Castelli G, Pelosi E, et al. Toxicities Associated with CAR-T Cell Therapies. Mediterr J Hematol Infect Dis 2025; 17: e2025039, DOI: 10.4084/MJHID.2025.039. eCollection 2025.
27.
Bakirova S, Baigenzhin A, Tuganbekova S, et al. Comparative Efficacy of Autologous Hematopoietic and Mesenchymal Stem Cell Transplantation in Patients with Systemic Sclerosis: A Systematic Review. J Clin Med 2025; 15: 261, DOI: 10.3390/jcm15010261.
28.
Sullivan KM. Hematopoietic stem cell transplant, chimeric antigen receptor T-cells, and other cellular therapies as stepping stones toward long-term improvement in severe scleroderma and other autoimmune diseases. Semin Arthritis Rheum 2025; 72S: 152676, DOI: 10.1016/j.semarthrit.2025.152676.
29.
Sieiro Santos C, Del Galdo F. New horizons in systemic sclerosis treatment: advances and emerging therapies in 2025. RMD Open 2025; 11: e005776, DOI: 10.1136/rmdopen-2025-005776.
30.
Conforti A, Cifuentes-González C, Ariani A, et al. CAR-T Cell Therapy in Autoimmune Diseases: Promise, Progress, and Pitfalls. Rheumato 2025; 5: 15, DOI: 10.3390/rheumato5040015.
31.
Xu X, Su SH. CAR-T cell therapies in autoimmune rheumatic diseases: a brief report on the clinical trial landscape, current status, and future perspectives. Front Immunol 2025; 16: 1630569, DOI: 10.3389/fimmu.2025.1630569.
32.
Li YR, Lyu Z, Chen Y, et al. Frontiers in CAR-T cell therapy for autoimmune diseases. Trends Pharmacol Sci 2024; 45: 839-857, DOI: 10.1016/j.tips.2024.07.005.
33.
Anyfanti P, Evangelidis P, Kotsiou N, et al. Chimeric Antigen Receptor T Cell Immunotherapy for Autoimmune Rheumatic Disorders: Where Are We Now? Cells 2025; 14: 1242, DOI: 10.3390/ cells14161242.
34.
Wu D, Xu-Monette ZY, Zhou J, et al. CAR T-cell therapy in autoimmune diseases: a promising frontier on the horizon. Front Immunol 2025; 16: 1613878, DOI: 10.3389/fimmu.2025.1613878.
35.
Lyu X, Gupta L, Tholouli E, et al. Chimeric antigen receptor T cell therapy: a new emerging landscape in autoimmune rheumatic diseases. Rheumatology (Oxford) 2024; 63: 1206–1216, DOI: 10.1093/rheumatology/kead616.
36.
Subklewe M, Magno G, Gebhardt C, et al. Application of blinatumomab, a bispecific anti-CD3/CD19 T-cell engager, in treating severe systemic sclerosis: A case study. Eur J Cancer 2024; 204: 114071, DOI: 10.1016/j.ejca.2024.114071.
Copyright: © Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (https://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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