In 2025, a new wave of ‘off-the-shelf’ B cell-depleting modalities for the treatment of autoimmune diseases emerged, encompassing allogeneic cellular therapies, in vivo chimeric antigen receptor engineering, and bispecific antibodies.
Key advances
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Allogeneic induced pluripotent stem cell-derived CD19–BCMA-targeting chimeric antigen receptor (CAR) natural killer cell therapy showed safety and strong efficacy in refractory systemic sclerosis2.
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A targeted lipid nanoparticle platform enables in vivo mRNA that generates functional CAR T cells, achieving effective tumour control and B cell depletion with immune system reset in pre-clinical models3.
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A 1-month course of the bispecific T cell engager teclistamab successfully induced deep B cell depletion and lasting drug-free remission in six of ten patients with refractory autoimmune diseases5.
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References
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Wang, X. et al. An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosis. Cell 188, 4225–4238 (2025).
Hunter, L. et al. In vivo CAR T cell generation to treat cancer and autoimmune disease. Science 388, 1311–1317 (2025).
Wang, Q. et al. In vivo CD19 CAR T-cell therapy for refractory systemic lupus erythematosus. N. Engl. J. Med. 393, 1542–1544 (2025).
Bucci, L. et al. BCMA T-cell engager therapy in patients with refractory autoimmune disease. N. Engl. J. Med. 393, 1544–1547 (2025).
Müller, F. et al. CD19 CAR T-cell therapy in multidrug-resistant ulcerative colitis. N. Engl. J. Med. 393, 1239–1241 (2025).
Hu, Z. et al. BCMA-targeted CAR T cell therapy can effectively induce disease remission in refractory lupus nephritis. Ann. Rheum. Dis. 84, 1675–1683 (2025).
Feng, J. et al. Co-infusion of CD19-targeting and BCMA-targeting CAR-T cells for treatment-refractory systemic lupus erythematosus: a phase 1 trial. Nat. Med. 31, 3725–3736 (2025).
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Xu, H. The dawn of ‘off-the-shelf’ B cell-depleting therapies for autoimmune diseases. Nat Rev Rheumatol 22, 78–79 (2026). https://doi.org/10.1038/s41584-025-01343-5
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DOI: https://doi.org/10.1038/s41584-025-01343-5
