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
英文原题:Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma.
Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma.
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靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)T细胞彻底改变了复发/难治性多发性骨髓瘤(RRMM)的治疗。然而,关于细胞(CAR)T细胞动力学及其与缓解、耐药或细胞因子释放综合征(CRS)发生之间关联的数据有限。
因此,我们对27例接受Idecabtagene vicleucel(Ide-cel)治疗的RRMM患者进行了全面的流式细胞术分析,以评估靶向BCMA的CAR-T 细胞的扩增能力、持久性及其对旁观者细胞的影响。
此外,我们还探讨了副作用,如细胞因子释放综合征(CRS)和血细胞减少。我们的结果表明,CD8+ CAR-T 细胞的体内扩增与缓解相关,然而持久性对于RRMM患者的持久缓解并非必需。
此外,我们的数据提供证据表明,在白细胞采集日CD8+ T细胞比例增加,结合成功的淋巴细胞清除,可对结局产生积极影响。我们表明,具有较高级别CRS风险的患者在淋巴细胞清除之前即可被识别。
我们广泛的表征有助于更好地理解靶向BCMA的CAR-T 细胞的动力学和效应,从而预测个体患者的缓解情况以及副作用,以便在早期阶段进行干预甚至预防。
B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM).
However, data on cellular (CAR) T cell dynamics and the association with response, resistance or the occurrence of cytokine release syndrome (CRS) are limited.
Therefore, we performed a comprehensive flow cytometry analysis of 27 RRMM patients treated with Idecabtagene vicleucel (Ide-cel) to assess the expansion capacity, persistence and effects on bystander cells of BCMA-targeting CAR T cells.
Additionally, we addressed side effects, like cytokine release syndrome (CRS) and cytopenia.
Our results show that in vivo expansion of CD8 + CAR T cells is correlated to response, however persistence is not essential for durable remission in RRMM patients.
In addition, our data provide evidence, that an increased fraction of CD8 + T cells at day of leukapheresis in combination with successful lymphodepletion positively influence the outcome.
We show that patients at risk for higher-grade CRS can be identified already prior to lymphodepletion.
Our extensive characterization contributes to a better understanding of the dynamics and effects of BCMA-targeting CAR T cells, in order to predict the response of individual patients as well as side effects, which can be counteracted at an early stage or even prevented.
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