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
从多发性骨髓瘤 CAR-T 细胞治疗后循环肿瘤 DNA 解析应答动态和治疗耐药
英文原题：Deciphering response dynamics and treatment resistance from circulating tumor DNA after CAR T-cells in multiple myeloma.
查看英文原题
Deciphering response dynamics and treatment resistance from circulating tumor DNA after CAR T-cells in multiple myeloma.
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中文摘要
尽管治疗取得了进展，多发性骨髓瘤（MM）仍是一种无法治愈的癌症，复发很常见。我们开发了一种循环肿瘤 DNA（ctDNA）方法，用于表征肿瘤基因组学、监测治疗反应并检测 MM 的早期复发。通过对来自 64 例新诊断或复发/难治性疾病患者的 412 份标本进行测序，我们证明了 ctDNA 与关键临床生物标志物以及患者结局之间的相关性。
我们进一步扩展了我们的方法，以在接受抗 BCMA CAR-T 细胞（BCMA-CAR）治疗的患者中同时追踪 CAR 特异性游离 DNA（CAR-cfDNA）。
我们证明，BCMA-CAR 后的 ctDNA 水平与相对进展时间（TTP）呈负相关，并且通过外周血 ctDNA（ctDNA-MRD）定量的可测量残留病（MRD）与临床骨髓 MRD 一致。
最后，我们表明 ctDNA-MRD 可以预测临床复发，并识别基因组学定义的治疗耐药克隆的出现。这些发现表明 ctDNA 在 MM 的分子特征描述和疾病监测中具有多种临床用途。
展开英文摘要原文
Despite advances in treatments, multiple myeloma (MM) remains an incurable cancer where relapse is common.
We developed a circulating tumor DNA (ctDNA) approach in order to characterize tumor genomics, monitor treatment response, and detect early relapse in MM. By sequencing 412 specimens from 64 patients with newly diagnosed or relapsed/refractory disease, we demonstrate the correlation between ctDNA and key clinical biomarkers, as well as patient outcomes.
We further extend our approach to simultaneously track CAR-specific cell-free DNA (CAR-cfDNA) in patients undergoing anti-BCMA CAR T-cell (BCMA-CAR) therapy.
We demonstrate that ctDNA levels following BCMA-CAR inversely correlate with relative time to progression (TTP), and that measurable residual disease (MRD) quantified by peripheral blood ctDNA (ctDNA-MRD) was concordant with clinical bone marrow MRD.
Finally, we show that ctDNA-MRD can anticipate clinical relapse and identify the emergence of genomically-defined therapy-resistant clones.
These findings suggest multiple clinical uses of ctDNA for MM in molecular characterization and disease surveillance.
论文信息
- 作者
- Hosoya H、Carleton M、Tanaka K、Sworder B、Syal S、Sahaf B、Maltos AM、Silva O
- 第一作者单位
- Division of Blood and Marrow Transplant and Cell Therapy, Department of Medicine, Stanford University, Stanford, CA, USA.United States
- 通讯作者单位
- Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA. dkurtz@stanford.edu.United States
- 期刊
- Nature communications2025 Feb 20
- 原文标识
- PubMed 39979252 · DOI 10.1038/s41467-025-56486-6
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