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脐带血:异体 CAR-T 细胞的有前景来源

英文原题:Umbilical cord blood: A promising source for allogeneic CAR-T cells.

查看英文原题

Umbilical cord blood: A promising source for allogeneic CAR-T cells.

PubMed 2022/07/29(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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中文摘要

CAR-T(CAR-T)细胞疗法是治疗复发/难治性急性淋巴细胞白血病(R/R ALL)的有效方法。然而,B-ALL患者来源的自体CAR-T 细胞常表现为扩增能力差、耗竭和无反应。异基因CAR-T 细胞可作为有效替代方案克服这些局限,但最佳替代细胞来源尚不清楚。

本研究在体外及NOD-Prkdcem26cd52Il2rgem26Cd22/Nju(NCG)免疫缺陷小鼠中,比较健康供者脐带血(CB)、健康供者外周血(PB)及B-ALL患者外周血[PB(患者)]来源抗CD19 CAR-T 细胞的免疫表型和抗肿瘤疗效。

结果显示,与PB(患者)来源CAR-T 相比,健康供者CB和PB来源CAR-T 中初始T细胞比例更高,在荷瘤小鼠中抑制肿瘤时间更长。PB(患者)来源CAR-T 中调节性T细胞(Treg)比例较高,并释放大量白细胞介素10(IL-10),也提示预后较差。

因此,健康供者来源CAR-T 抗肿瘤疗效优于患者PB来源CAR-T,而CB可能是异基因CAR-T 细胞的良好来源。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed and refractory acute lymphoblastic leukemia (R/R ALL).

However, autologous CAR-T cells derived from patients with B-ALL often show poor amplification ability, exhaustion, and anergy. To overcome these limitations, allogeneic CAR-T cells may be used as effective substitutes; however, which source would be the best substitute is unclear. In this study, we compared the immunophenotype and antitumor efficacy of anti-CD19 CAR-T cells derived from healthy donor cord blood (CB), healthy donor peripheral blood (PB), and PB of B-ALL patients [PB (patient)] in vitro and NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG)-immunodeficient mice, respectively.

The results revealed that CAR-T cells derived from healthy donor CB and PB showed a higher proportion of naive T cells and longer tumor suppression in tumor-bearing mice than those of PB (patient). PB (patient) CAR-T cells had a higher proportion of regulatory T cells (Treg cells) and released high levels of interluekin-10 (IL-10), which also suggest a poor prognosis.

Thus, CAR-T cells derived from healthy donors have better antitumor efficacy than CAR-T cells derived from PB (patient), and CB may be a good source of allogeneic CAR-T cells.

论文信息

作者
Liu DD、Hong WC、Qiu KY、Li XY、Liu Y、Zhu LW、Lai WX、Chen H
单位
Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.China
期刊
Frontiers in oncology2022
原文标识
PubMed 35965561 · DOI 10.3389/fonc.2022.944248