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| Item Type: | Article |
|---|---|
| Title: | Single-cell profiling of immune reset in patients with refractory generalized myasthenia gravis receiving autologous CD19/BCMA CAR-T cell therapy |
| Creators Name: | Ruan, Zhe, Ning, Fan, Zhang, Wenyan, Li, Shuang, Su, Yue, Tang, Yonglan, Cao, Xiangqi, Huang, Xiaoxi, Song, Na, Li, Zhuyi, Li, Hang, Luan, Xiao, Yang, Naibo, Li, Ying, Paul, Friedemann, Liu, Qiang and Chang, Ting |
| Abstract: | BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting CD19 or B cell maturation antigen (BCMA) hold great promise to treat neuroimmune disorders, but the efficacy of CD19/BCMA dual-targeting CAR-T cells and their impact on systemic immunity are poorly understood. METHODS: In this phase 1 study (ClinicalTrials.gov: NCT06371040), patients with refractory generalized myasthenia gravis (gMG) received autologous CD19/BCMA CAR-T cells without prior lymphodepletion. The primary endpoint was the frequency and severity of treatment-emergent adverse events at week 4. Secondary endpoints included changes in MG-specific scale scores. Single-cell RNA sequencing and flow cytometry were performed to characterize longitudinal changes in B cell, plasma cell, and T cell compartments following CAR-T cell infusion. FINDINGS: CD19/BCMA CAR-T cells expanded in vivo, leading to depletion of B cells and plasma cells. All six patients had a favorable safety profile. Minimal symptom expression (MG Activities of Daily Living Score [MG-ADL] = 0) was achieved in five patients by day 90, with responses sustained through day 120–150, and all patients discontinued glucocorticoids while reducing immunosuppressant use. Immune profiling revealed a transient decline in memory B cells and plasma cells. The repopulated B cells exhibited attenuated B cell receptor signaling and increased inhibitory signals derived from bone marrow niche cells. Further, clonal expansion of T and B cells was significantly reduced. CONCLUSIONS: CD19/BCMA CAR-T cell therapy is safe and effective in refractory gMG without lymphodepletion, leading to systemic immune reset that warrants future investigations in larger clinical trials. FUNDING: This study was supported by the National Key Research and Development Program and the National Natural Science Foundation of China. |
| Source: | Med |
| ISSN: | 2666-6359 |
| Publisher: | Elsevier / Cell Press |
| Page Range: | 101026 |
| Date: | 25 February 2026 |
| Official Publication: | https://doi.org/10.1016/j.medj.2026.101026 |
| PubMed: | View item in PubMed |
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