Cell Therapy Group, Maimonides Institute for Biomedical Research, 14004 Córdoba, Spain.
Department of Hematology, Reina Sofia University Hospital, 14004 Córdoba, Spain.
Int J Mol Sci. 2024 May 25;25(11):5769. doi: 10.3390/ijms25115769.
Lymphocyte collection by apheresis for CAR-T production usually does not include blood mobilized using granulocyte colony stimulating factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinics, makes it necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent works that experimentally verify the role and functionality of T and NK lymphocytes and the generation of CAR-T from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant, and the different sub-populations remain stable. In addition, the expansion and proliferation rates are invariant regardless of mobilization with G-CSF as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.
通过单采术从外周血中采集 CAR-T 生产用淋巴细胞通常不包括使用粒细胞集落刺激因子 (G-CSF) 动员的血液,因为人们普遍认为它会导致淋巴细胞数量和功能下降。然而,它被用于干细胞移植,这是治疗血液系统恶性肿瘤的常见方法。CAR 疗法(CAR-T 和 NK-CAR)的需求不断增长,无论是在研究还是临床中,都有必要评估动员后的 PBSC 产品是否可能成为此类疗法的潜在候选物。这篇综述收集了最近的实验工作,这些工作验证了 G-CSF 动员后从单采术获得的 T 和 NK 淋巴细胞以及 CAR-T 的产生的作用和功能。如前所述,T 细胞在表型上没有显著差异,CD4+和 CD8+的比例保持不变,不同的亚群保持稳定。此外,无论是否用 G-CSF 动员,细胞的扩增和增殖率以及促炎细胞因子的分泌和细胞毒性能力都保持不变。因此,推测在单采术之前动员的细胞是用于过继性治疗的 T 细胞的新替代来源,这将有助于缓解高需求、增加可用性,并利用大量现有的冷冻保存产品。