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脐带血作为分化程度较低 T 细胞的来源以产生 CD123 CAR-T 细胞

英文原题:Umbilical Cord Blood as a Source of Less Differentiated T Cells to Produce CD123 CAR-T Cells.

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Umbilical Cord Blood as a Source of Less Differentiated T Cells to Produce CD123 CAR-T Cells.

PubMed 2022/06/28(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)疗法已使白血病和淋巴瘤患者取得显著成功。脐带血(UCB)储存于脐带血库,是生产CAR-T 细胞的一种有吸引力的T细胞来源。我们采用此前以成人外周血(PB)开发的第三代CD123 CAR-T(CD28/4-1BB),测试能否利用新鲜或冻存UCB制备CD123 CAR-T 细胞。所得细胞产品具有高且稳定的转导效率,CAR-T 细胞分化程度较低,同时体内外细胞毒功能保持较高。此外,冻存UCB制备的CAR-T 与新鲜UCB制备的CAR-T 功能相当。总体而言,这些数据为UCB来源CAR-T 临床开发铺平道路。UCB CAR-T 可在自体情境下(UCB移植后)回输以减少移植后复发,也可用于异基因环境;由于HLA限制较少,供者与受者配型要求更宽松。

展开英文摘要原文

Chimeric Antigen Receptor (CAR) therapy has led to great successes in patients with leukemia and lymphoma. Umbilical Cord Blood (UCB), stored in UCB banks, is an attractive source of T cells for CAR-T production.

We used a third generation CD123 CAR-T (CD28/4-1BB), which was previously developed using an adult's Peripheral Blood (PB), to test the ability of obtaining CD123 CAR-T from fresh or cryopreserved UCB.

We obtained a cell product with a high and stable transduction efficacy, and a poorly differentiated phenotype of CAR-T cells, while retaining high cytotoxic functions in vitro and in vivo.

Moreover, CAR-T produced from cryopreserved UCB are as functional as CAR-T produced from fresh UCB.

Overall, these data pave the way for the clinical development of UCB-derived CAR-T. UCB CAR-T could be transferred in an autologous manner (after an UCB transplant) to reduce post-transplant relapses, or in an allogeneic setting, thanks to fewer HLA restrictions which ease the requirements for a match between the donor and recipient.

论文信息

作者
Caël B、Galaine J、Bardey I、Marton C、Fredon M、Biichle S、Poussard M、Godet Y
单位
RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, EFS BFC, INSERM, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.France
期刊
Cancers2022 Jun 28
原文标识
PubMed 35804941 · DOI 10.3390/cancers14133168