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产量驱动策略优化淋巴瘤患者 CD19 CAR-T 细胞治疗的采集

英文原题:Yield-driven approach optimizes apheresis of CD19 chimeric antigen receptor-T cell therapy for patients with lymphoma.

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Yield-driven approach optimizes apheresis of CD19 chimeric antigen receptor-T cell therapy for patients with lymphoma.

PubMed 2025/06/06(内容时间) Cytotherapy Q1 · IF 4.5(JCR 2025)

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中文摘要

为嵌合抗原受体(CAR)T细胞治疗进行的白细胞单采需要根据产品特定的生产要求进行优化。我们回顾性分析了2022年1月至2024年10月期间在京都大学医院接受白细胞单采以制备tisagenlecleucel(tisa-cel,n = 31)、lisocabtagene maraleucel(liso-cel,n = 29)或axicabtagene ciloleucel(axi-cel,n = 20)的80例大B细胞淋巴瘤患者。白细胞单采前外周血(PB)CD3 + 细胞计数(中位数,504/ L)和采集效率(中位数,62.1%)在各组间相似。axi-cel组需要显著更大的处理血容量(axi-cel,12 L;liso-cel,12 L;tisa-cel,10 L;P < 0.001)和更长的处理时间(axi-cel,240 min;liso-cel,204 min;tisa-cel,203 min;P = 0.002),从而导致更高的CD3 + 细胞产量。

此外,axi-cel组CD3 + 细胞产量的标准差显著更大(axi-cel,3.04 10 9 cells;liso-cel,1.54 10 9 cells;tisa-cel,1.59 10 9 cells;P = 0.003)。axi-cel组更频繁地超过达到5 10 9 CD3 + 细胞所需的估计血容量(axi-cel,45.0%;liso-cel,17.2%;tisa-cel,16.1%;P = 0.048)。这些发现凸显了不同CAR-T 产品之间白细胞单采程序的可变性。基于PB细胞计数以细胞产量为目标的方案可以优化所需处理的血容量,从而减轻患者负担。

展开英文摘要原文

Leukapheresis for chimeric antigen receptor (CAR) T cell therapy requires optimization according to product-specific manufacturing requirements.

We retrospectively analyzed 80 patients with large B-cell lymphoma, who underwent leukapheresis for tisagenlecleucel (tisa-cel, n = 31), lisocabtagene maraleucel (liso-cel, n = 29) or axicabtagene ciloleucel (axi-cel, n = 20) at Kyoto University Hospital between January 2022 and October 2024. Peripheral blood (PB) CD3 + cell counts before leukapheresis (median, 504/ L) and collection efficiencies (median, 62.

1%) were similar among groups. The axi-cel group required significantly larger processing blood volumes (axi-cel, 12 L; liso-cel, 12 L; tisa-cel, 10 L; P < 0. 001) and longer processing times (axi-cel, 240 min; liso-cel, 204 min; tisa-cel, 203 min; P = 0. 002), resulting in higher CD3 + cell yields.

Moreover, the standard deviation of CD3 + cell yields was significantly larger in the axi-cel group (axi-cel, 3. 04 10 9 cells; liso-cel, 1. 54 10 9 cells; tisa-cel, 1. 59 10 9 cells; P = 0. 003). The axi-cel group more frequently exceeded estimated blood volumes needed to achieve 5 10 9 CD3 + cells (axi-cel, 45. 0%; liso-cel, 17. 2%; tisa-cel, 16. 1%; P = 0. 048).

These findings highlight variability in leukapheresis procedures among CAR-T products. Protocols targeting cell yields based on PB cell counts may optimize blood volume to be processed so as to reduce patient burden.

论文信息

作者
Jo T、Kitawaki T、Sakamoto T、Mizumoto C、Kanda J、Nishikori M、Yamashita K、Nagao M
单位
Department of Cytotherapy, Kyoto University Hospital, Kyoto, Japan; Department of Hematology, Kyoto University Hospital, Kyoto, Japan; Center for Research and Application of Cellular Therapy, Kyoto University Hospital, Kyoto, Japan. Electronic address: tjoh@kuhp.kyoto-u.ac.jp.Japan
期刊
Cytotherapy2025 Oct
原文标识
PubMed 40590814 · DOI 10.1016/j.jcyt.2025.06.002