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:Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy.
Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy.
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CAR-T 制备所需淋巴细胞通常通过单采收集,且一般不纳入经粒细胞集落刺激因子(G-CSF)动员的血液细胞,因为人们普遍认为 G-CSF 会降低淋巴细胞数量和功能。
不过,G-CSF 动员常用于干细胞移植,而后者是血液系统恶性肿瘤的常见治疗。研究和临床中 CAR 疗法(CAR-T 和 NK-CAR)需求不断增长,因此有必要评估动员外周血干细胞(PBSC)产品是否可用于此类疗法。本综述汇集近期实验验证的研究,介绍 G-CSF 动员后单采所得 T 和 NK 淋巴细胞的作用与功能,以及由此制备 CAR-T 细胞的情况。如文中所述,T 细胞表型变化不明显,CD4+ 与 CD8+ 比例保持稳定,不同亚群也维持稳定。
此外,无论是否经过 G-CSF 动员,细胞扩增和增殖速率均无变化,促炎性细胞因子分泌和细胞毒能力也不变。因此,单采前动员所得细胞被认为是过继疗法的新型 T 细胞来源,可缓解高需求、增加可及性,并利用现有大量冻存产品。
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.
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