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:(CAR-)T cell dynamics following chimeric antigen receptor T cells for large B cell lymphoma: a translational tale.
(CAR-)T cell dynamics following chimeric antigen receptor T cells for large B cell lymphoma: a translational tale.
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嵌合抗原受体(CAR)T细胞疗法是B细胞恶性肿瘤治疗的一项突破。CAR-T 细胞输注通常 preceded by 一个化疗方案,其淋巴清除特性为工程化T细胞的扩增创造了有利环境。虽然这一过程看似简单,但新出现的证据表明,复杂的机制——共同代表CAR-T 细胞输注后的免疫动力学——影响CAR-T 细胞的行为。在输注前,最终产品中富含应激较少的CAR-T 细胞可以改善其扩增和持久性,为早期单采和给药提供了生物学依据。输注后,功能失调的CAR-T 亚群的出现,如调节性CAR-T 或NK样CAR-T 细胞,可能损害疗效。非CAR转导T细胞的恢复增加了进一步的复杂性,因为这些细胞可能影响结局或加剧并发症,如感染或持续性血细胞减少。在这篇综述中,我们总结了关于大B细胞淋巴瘤CAR-T 细胞输注后免疫动力学理解的最新进展,重点关注CAR工程化和天然T细胞群体,以及它们对治疗效果和患者结局的影响。
Chimeric antigen receptor (CAR) T-cell therapy represents a breakthrough in the treatment of B-cell malignancies. CAR-T cells infusion generally follows a chemotherapy regimen whose lymphodepleting properties create a favorable environment for the expansion of engineered T cells. While this process appears straightforward, emerging evidence reveals that complex mechanisms, collectively representing immune dynamics following CAR-T cell infusion, influence CAR-T cells behavior. In advance of infusion, a final-product enriched with less stressed CAR-T cells can improve their expansion and persistence, providing a biological rationale for early apheresis and administration.
Following infusion, the emergence of dysfunctional CAR-T subpopulations, like regulatory or NK-like CAR-T cells, can impair efficacy. The recovery of non-CAR transduced T cells adds further complexity, as these cells could either impact outcomes or exacerbate complications, such as infections or prolonged cytopenia.
In this review, we summarize the latest advances in understanding the immune dynamics following CAR-T cell infusion for large B-cell lymphomas, with a focus on both CAR-engineered and native T cell populations, and their impact on treatment efficacy and patient outcomes.
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