CAR-T-Zellen zur Therapie von Autoimmunerkrankungen

Die CAR-T-Zell-Therapie hat die Behandlung von Leukämien und Lymphomen der B-Zellreihe revolutioniert. Eine Nebenwirkung ist die Depletion von B-Zellen. Diese unerwünschte Nebenwirkung könnte sich als therapeutisches Prinzip für Autoimmunerkrankungen erweisen, die durch aberrante B-Zellen verursacht werden. So zeigen jüngste Entwicklungen, dass CAR-T-Zellen bei therapierefraktären Autoimmunerkrankungen vielversprechende Ergebnisse erzielen können.

Abstract

Originally developed for hematologic malignancies, chimeric antigen receptor (CAR) T-cell therapy is now emerging as a promising treatment option for severe autoimmune diseases. The foundational principle of targeted B-cell depletion has shown transformative potential in cases where autoimmunity is driven by pathogenic B-cell subsets. Unlike monoclonal antibodies, CAR T cells actively penetrate tissue, persist long-term, and eliminate both circulating and tissue-resident B cells. Early clinical trials, particularly those involving CD19-directed CAR T cells, have demonstrated long-lasting remissions in patients with diseases such as systemic lupus erythematosus (SLE), myasthenia gravis, and systemic sclerosis.

Notably, the toxicity profile of CAR T-cell therapy for autoimmune diseases appears significantly more favorable than for oncological diseases. Severe cytokine release syndrome (CRS) and neurotoxicity (ICANS) are rare, and B-cell reconstitution typically occurs within three to four months without disease relapse. This supports the hypothesis of an “immune reset.” The rapid clinical and immunologic recovery distinguishes autoimmune indications from malignant ones, suggesting a different therapeutic dynamic.

However, challenges remain, particularly the cost and logistical complexity of autologous CAR T-cell production. However, allogeneic “off-the-shelf” products are under active investigation. With over 100 ongoing clinical trials, CAR T-cell therapy is poised to transform the treatment of autoimmunity. This novel approach may provide long-term immunologic tolerance where conventional immunosuppression fails.

Schlüsselwörter

CAR-T-Zellen - Autoimmunerkrankungen - B-Zellen - Immunologischer Neustart - Zelltherapie

Keywords

CAR T-cells - autoimmune diseases - immune reset

Publication History

Article published online:
12 August 2025

• Literatur

• 1 June CH, O'Connor RS, Kawalekar OU. et al. CAR T cell immunotherapy for human cancer. Science 2018; 359: 1361-1365
• 2 Melenhorst JJ, Chen GM, Wang M. et al. Decade-long leukaemia remissions with persistence of CD4(+) CAR T cells. Nature 2022; 602: 503-509
• 3 Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 2016; 127: 3321-3330
• 4 Rejeski K, Perez A, Sesques P. et al. CAR-HEMATOTOX: a model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood 2021; 138: 2499-2513
• 5 Cordas Dos Santos DM, Tix T, Shouval R. et al. A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy. Nat Med 2024; 30: 2667-2678
• 6 Baker DJ, Levine BL, June CH. Assessing the oncogenic risk: the long-term safety of autologous chimeric antigen receptor T cells. Lancet 2025; 405: 751-754
• 7 Lee DSW, Rojas OL, Gommerman JL. B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat Rev Drug Discov 2021; 20: 179-199
• 8 Kamburova EG, Koenen HJ, Borgman KJ. et al. A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function. Am J Transplant 2013; 13: 1503-1511
• 9 Mougiakakos D, Meyer E, Schett G. CAR T-cells in autoimmunity: game changer or stepping stone?. Blood 2025; 145: 1841-1849
• 10 Mougiakakos D, Kronke G, Volkl S. et al. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med 2021; 385: 567-569
• 11 Muller 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
• 12 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: 615-624
• 13 Fischbach F, Richter J, Pfeffer LK. et al. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med 2024; 5: 550.e2-558.e2
• 14 Qin C, Tian DS, Zhou LQ. 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 Transduct Target Ther 2023; 8: 5
• 15 Trautmann-Grill K, von Bonin M, Georgi A. et al. Salvage treatment of multi-refractory primary immune thrombocytopenia with CD19 CAR T cells. Lancet 2025; 405: 25-28
• 16 Granit V, Benatar M, Kurtoglu M. 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 Neurol 2023; 22: 578-590