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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prevalence of CCR7-Positive CD8 T Cells as a Prognostic Factor in B-Cell Maturation Antigen -Targeted Chimeric Antigen Receptor T Cell Therapy.
Prevalence of CCR7-Positive CD8 T Cells as a Prognostic Factor in B-Cell Maturation Antigen -Targeted Chimeric Antigen Receptor T Cell Therapy.
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未来,我们的结果将有助于筛选出可能获得更有利结局的特定患者,并应有助于为 RRMM 中的 CAR-T 细胞治疗建立最佳应用策略。
CAR-T(CAR-T)细胞疗法可有效治疗复发/难治性多发性骨髓瘤(RRMM);然而,B细胞成熟抗原(BCMA)CAR-T 细胞疗法后复发与不良结局相关。因此,需要能够预测结局的适当生物标志物。
接受靶向BCMA的CAR-T 细胞疗法伊德卡布他基因维克乐的患者,根据无进展生存期(PFS)事件发生时间180天的截点分为两组。
短期应答组患者诊断时年龄较大,从诊断到单采的时间较短,既往接受双特异性抗体治疗或含烷化剂化疗的比例更高,而单采前即刻接受免疫调节药物方案化疗的比例较低。长期应答组的单采样本中,CD8阳性初始型或干细胞记忆型(CCR7+ CD45RO−)及中央记忆型(CCR7+ CD45RO+)T细胞比例显著较高。将这两个T细胞亚群合并为CCR7阳性CD8 T细胞后发现,CCR7阳性CD8 T细胞水平较高的患者PFS显著更佳。
未来,我们的研究结果有助于筛选更可能获得良好结局的特定患者,并有望为建立RRMM CAR-T 细胞疗法的最佳应用策略作出贡献。
Chimeric antigen receptor T (CAR-T) cell therapy is effective for relapsed or refractory multiple myeloma (RRMM); however, relapse after the B-cell maturation antigen (BCMA) CAR-T cell therapy is associated with poor outcome. Hence, appropriate biomarkers that can predict the outcome are needed.
Patients who received idecabtagene vicleucel, a BCMA-targeted CAR-T cell therapy, were divided into two groups according to a cut-off value of 180 days for the progression-free survival (PFS) event.
Patients in the short responder group were older at diagnosis, had a shorter time from diagnosis to apheresis, and more frequently had prior bispecific antibody treatment or alkylator-containing chemotherapies, while they received less immunomodulatory drugs-based chemotherapy just prior to apheresis. Apheresis samples collected from the long responder group had significantly higher proportion of CD8-positive na ve or stem cell memory (CCR7 + CD45RO - ) or central memory (CCR7 + CD45RO + ) T cells. When these two T cell subsets were combined into CCR7-positive CD8 T cells, the patients with high levels of CCR7-positive CD8 T cells showed significantly better PFS.
In the future, our results will help us to select specific patients that are likely to have a more favorable outcome and should contribute to establishing an optimal application strategy for CAR-T cell therapies in RRMM.
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