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:Immune reconstitution following allogeneic hematopoietic cell transplantation and CAR-T therapy: dynamics, determinants, and directions.
Immune reconstitution following allogeneic hematopoietic cell transplantation and CAR-T therapy: dynamics, determinants, and directions.
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免疫重建(IR)是异基因造血细胞移植(allo-HCT)和细胞治疗后发生的一个动态且序贯的过程,涉及固有免疫和适应性免疫区室的逐步恢复。IR的成功是临床结局的关键决定因素,包括移植物抗宿主病和移植物抗白血病效应的风险。在allo-HCT的背景下,IR受多种因素影响,包括移植方式、预处理方案、治疗干预和移植后策略。CAR-T 细胞治疗后IR的动力学和质量也受多种因素影响,如淋巴细胞清除性化疗、CAR构建体设计和患者的基线免疫状态。特别是,靶向B细胞的CAR-T 治疗常导致B细胞再生障碍、低丙种球蛋白血症和免疫耗竭,需要改进监测和治疗后干预。这些免疫学效应凸显了改进治疗后监测和支持性干预的必要性,以降低感染风险并确保持续的免疫恢复。为了更好地表征allo-HCT和CAR-T 环境中的IR,先进的免疫分析技术,如流式细胞术和单细胞RNA测序,正在为免疫恢复的动态提供新的见解。
在此,我们总结了关于IR动力学的当前知识,并评估了不同移植和CAR-T 环境的影响。然后,我们讨论了优化allo-HCT和CAR-T 治疗接受者免疫监测和治疗方法的个性化策略。
Immune reconstitution (IR) is a dynamic and sequential process that occurs after allogeneic hematopoietic cell transplantation (allo-HCT) and cellular therapies, involving the gradual recovery of both innate and adaptive immune compartments. The success of IR is a critical determinant of clinical outcomes, including the risk of graft-versus-host disease and graft-versus-leukemia effects. In the context of allo-HCT, IR shaped by various factors, including transplantation modalities, conditioning regimens, therapeutic interventions, and post-transplant strategies. The kinetics and quality of IR following chimeric antigen receptor T-cell (CAR-T) therapy are also shaped by several factors, such as lymphodepleting chemotherapy, CAR construct design, and the patient's baseline immune status.
In particular, B-cell-targeted CAR-T therapy frequently results in B-cell aplasia, hypogammaglobulinemia, and immune exhaustion, necessitating improved monitoring and post-treatment interventions. These immunologic effects highlight the need for improved post-treatment monitoring and supportive interventions to reduce infection risk and ensure sustained immune recovery.
To better characterize IR across both allo-HCT and CAR-T settings, advanced immune profiling technologies, such as flow cytometry and single-cell RNA sequencing, are providing new insights into the dynamics of immune recovery.
Here, we summarize current knowledge on IR kinetics and evaluate the impact of different transplant and CAR-T settings.
We then discuss personalized strategies to optimize immune monitoring and therapeutic approaches for recipients of allo-HCT and CAR-T therapies.
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