Advances in gene, protein and cellular engineering provide unprecedented opportunities to redirect immune cells to treat autoimmunity. In 2023, novel cellular and precision immunotherapies showed remarkable promise in the treatment of rheumatic diseases.
Key advances
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B cell-targeted CAR T cell therapies can achieve prolonged clinical remission in various autoimmune diseases2,5.
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Precision cellular therapies hold promise for selective, antigen-specific elimination of autoreactive B cells6.
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TCR β-chain variable (TRBV)-targeted antibodies also show potential in T cell-mediated rheumatic diseases10.
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References
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Qin, C. 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. 8, 5 (2023).
Oh, S. et al. Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat. Biotechnol. 41, 1229–1238 (2023).
Britanova, O. V. et al. Targeted depletion of TRBV9+ T cells as immunotherapy in a patient with ankylosing spondylitis. Nat. Med. 29, 2731–2736 (2023).
Pecher, A.-C. et al. CD19-targeting CAR T cells for myositis and interstitial lung disease associated with antisynthetase syndrome. J. Am. Med. Assoc. 329, 2154–2162 (2023).
Cortés Hernández, J. et al. An open-label, multicenter, phase 1/2 study to assess safety, efficacy and cellular kinetics of YTB323, a rapid manufacturing CAR-T cell therapy targeting CD19 on B cells, for severe refractory systemic lupus erythematosus: preliminary results [abstract]. Arthritis Rheumatol. 75, suppl 9 (2023).
Feng, J., Hu, Y., Chang, A. H. & Huang, H. CD19/BCMA CAR-T cell therapy for refractory systemic lupus erythematosus - safety and preliminary efficacy data from a phase i clinical study. Blood 142, 4835–4835 (2023).
Yuan, Y. et al. Novel BCMA-CD19 compound CAR-T (cCAR) targets B cells and plasma cells achieving immune reset and eliminates all autoantibodies in systemic lupus erythematosus (SLE) and lupus nephritis (LN) patients resulting in long-term, medication-free remission [abstract]. Arthritis Rheumatol. 75, suppl 9 (2023).
Mog, B. et al. Chimeric autoantigen-T cell receptor (CATCR)-T cell therapies to selectively target autoreactive B cells [abstract]. Arthritis Rheumatol. 74, suppl 9 (2022).
Paul, S. et al. TCR β chain–directed bispecific antibodies for the treatment of T cell cancers. Sci. Transl. Med. 13, eabd3595 (2021).
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M.F.K. is a consultant to Argenx, Atara Biotherapeutics, Revel Pharmaceuticals, Sana Biotechnology and Sanofi. M.F.K. declares that he and The Johns Hopkins University have filed patent applications related to chimeric autoantigen-T cell receptor-T cell therapies and TCR region-targeting approaches.
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Konig, M.F. The rise of precision cellular therapies. Nat Rev Rheumatol 20, 69–70 (2024). https://doi.org/10.1038/s41584-023-01073-6
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DOI: https://doi.org/10.1038/s41584-023-01073-6