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简要研究报告:深度免疫表型分析揭示 CD19 CAR-T 细胞随时间的稳定性

英文原题:Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time.

查看英文原题

Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time.

PubMed 2024/01/22(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

变异性或稳定性可能对CD19 CAR-T 细胞的治疗成功和毒性产生影响。我们开展了一项前瞻性观察性研究,纳入12例接受Tisagenlecleucel治疗CD19+ B细胞恶性肿瘤的患者。使用31色光谱流式细胞术panel,我们分析了CAR-T 细胞输注前以及6个月随访期间纵向的CAR-T 细胞亚群分化阶段和耗竭标志物。CAR-T 细胞上的大多数活化标志物随时间显示出稳定的表达模式,且与治疗反应或毒性无关。无监督聚类分析揭示了与免疫细胞相关神经毒性综合征发生相关的CAR-T 细胞产品的免疫特征。值得在独立患者队列中验证,CAR-T 细胞产品的深入表型分析以及细胞输注后的纵向监测可能成为提高CAR-T 细胞治疗疗效和安全性的有价值工具。

展开英文摘要原文

Variability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells.

We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19 + B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation stages and exhaustion markers of CAR T-cell subsets prior to CAR T-cell infusion and longitudinally during 6 months of follow-up. The majority of activation markers on CAR T-cells showed stable expression patterns over time and were not associated with response to therapy or toxicity.

Unsupervised cluster analysis revealed an immune signature of CAR T-cell products associated with the development of immune cell-associated neurotoxicity syndrome. Warranting validation in an independent patient cohort, in-depth phenotyping of CAR T-cell products as well as longitudinal monitoring post cell transfer might become a valuable tool to increase efficacy and safety of CAR T-cell therapy.

论文信息

作者
Odak I、Bayir LM、Riemann L、Sikora R、Schneider J、Xiao Y、Möhn N、Skripuletz T
单位
Institute of Immunology, Hannover Medical School, Hannover, Germany.Germany
文献类型
观察性研究 · 非美国政府资助研究
期刊
Frontiers in immunology2024
原文标识
PubMed 38318174 · DOI 10.3389/fimmu.2024.1298598