CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
预测多发性骨髓瘤 BCMA 靶向 CAR-T 细胞治疗后结局与毒性的纵向单细胞图谱
英文原题：A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma.
查看英文原题
A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma.
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中文摘要
靶向B细胞成熟抗原（BCMA）的嵌合抗原受体（CAR）T细胞疗法正在改变复发/难治性多发性骨髓瘤（RRMM）的治疗格局。
我们分析了61例接受idecabtagene vicleucel（Ide-cel；n = 34）或ciltacabtagene autoleucel（Cilta-cel；n = 27）治疗的RRMM患者，发现Cilta-cel获得更高的完全缓解（CR）率（78% vs. 38%）以及更长的无进展生存期。利用涵盖135份血液样本的纵向单细胞多组学图谱，我们显示Cilta-cel诱导CD4 + 细胞毒性T细胞扩增，这一扩增与CR及免疫相关毒性相关，而非CR患者的CD8 + T细胞则表现出效应程序受损。在非B细胞中，浆细胞样树突状细胞（pDC）显示出最高的BCMA表达，且BCMA靶向药物可清除母细胞性浆细胞样树突状细胞肿瘤细胞系，提示该疾病的一种新治疗途径。可溶性BCMA降幅更大与CAR-T 扩增增强及全身性炎症相关。这些发现揭示了驱动BCMA导向免疫治疗疗效与毒性差异的细胞机制。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cell therapies targeting B cell maturation antigen (BCMA) are transforming treatment for relapsed or refractory multiple myeloma (RRMM).
We analyze 61 RRMM patients receiving idecabtagene vicleucel (Ide-cel; n = 34) or ciltacabtagene autoleucel (Cilta-cel; n = 27) and find that Cilta-cel achieves higher complete response (CR) rates (78% vs. 38%) and longer progression-free survival. Using a longitudinal single-cell multi-omics atlas of 135 blood samples, we show that Cilta-cel induces expansion of CD4 + cytotoxic T cells associated with CR and immune-related toxicities, whereas non-CR CD8 + T cells display impaired effector programs.
Among non-B cells, plasmacytoid dendritic cells (pDCs) show the highest BCMA expression and BCMA-targeted agents eradicate a blastic plasmacytoid dendritic cell neoplasm line, suggesting a novel therapeutic avenue for this disease. Greater reductions in soluble BCMA correlate with enhanced CAR T expansion and systemic inflammation.
These findings reveal cellular mechanisms driving differential efficacy and toxicity of BCMA-directed immunotherapy.
论文信息
- 作者
- Rade M、Fandrei D、Kreuz M、Seiffert S、Grahnert A、Friedrich M、Wiemers T、Born P
- 第一作者单位
- Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany.Germany
- 通讯作者单位
- Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany; Department of Hematology, Cell Therapy and Hemostaseology, University Hospital of Leipzig, Leipzig, Germany; Cancer Center Central Germany (CCCG) Leipzig-Jena, University Hospital of Leipzig, Leipzig, Germany; Myeloma and Cellular Therapy Services, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: merzm@mskcc.org.Germany
- 期刊
- Cancer cell2026 Mar 9
- 原文标识
- PubMed 41349540 · DOI 10.1016/j.ccell.2025.10.014