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嵌合抗原受体修饰 T 细胞过继免疫疗法治疗 CD19 阳性肿瘤的疗效和安全性:I 期临床试验的系统评价。

Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials.

机构信息

Division of Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, PR China.

出版信息

Leuk Lymphoma. 2013 Feb;54(2):255-60. doi: 10.3109/10428194.2012.715350. Epub 2012 Sep 8.


DOI:10.3109/10428194.2012.715350
PMID:22897728
Abstract

There remain some key questions regarding the adoptive infusion of chimeric antigen receptor (CAR) transduced T-cells in the clinical setting. This article systematically reviews the phase I clinical trials using CARs targeting CD19 in B-lineage malignancies. Twenty-nine patients were enrolled and the 6-month progression free survival for this cohort was 50.0 ± 9.9%. Univariate analysis showed that patients benefited from lymphodepletion before CAR+T-cell infusion and the administration of interleukin-2 (IL-2). Longer-term persistence (≥ 4 weeks) and stronger expansion of CAR+ T-cells in the blood and higher peak serum interferon-γ (IFN-γ) level (≥ 200 pg/mL) were also related to superior outcome. Regarding treatment-related adverse events, the most prominent toxicities were fever, rigors, chills, acute renal failure, hypotension and capillary leak syndrome. In conclusion, anti-CD19 CAR+ T-cells have shown some benefits in patients with B-lineage malignancies and are well tolerated in most patients. Preconditioning and cytokine supplement are required to improve the clinical outcome.

摘要

关于嵌合抗原受体(CAR)修饰的 T 细胞过继输注在临床环境中的应用仍存在一些关键问题。本文系统综述了靶向 B 细胞恶性肿瘤 CD19 的 CAR 的 I 期临床试验。共纳入 29 例患者,该队列的 6 个月无进展生存率为 50.0±9.9%。单因素分析显示,患者在接受 CAR+T 细胞输注前接受淋巴细胞耗竭治疗以及白细胞介素-2(IL-2)治疗可获益。CAR+T 细胞在血液中持续时间更长(≥4 周)和扩增更强,以及血清干扰素-γ(IFN-γ)峰值水平更高(≥200pg/mL)也与更好的结果相关。关于治疗相关的不良反应,最突出的毒性是发热、寒战、发冷、急性肾衰竭、低血压和毛细血管渗漏综合征。总之,抗 CD19 CAR+T 细胞在 B 细胞恶性肿瘤患者中显示出一定的益处,并且大多数患者均可耐受。需要预处理和细胞因子补充来改善临床结局。

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Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials.

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引用本文的文献

[1]
CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.

Nat Rev Gastroenterol Hepatol. 2025-4-14

[2]
Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.

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[3]
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Cancers (Basel). 2022-3-24

[4]
Acute kidney injury in cancer patients.

Clin Exp Nephrol. 2022-2

[5]
Survival outcomes and efficacy of autologous CD19 chimeric antigen receptor-T cell therapy in the patient with diagnosed hematological malignancies: a systematic review and meta-analysis.

Ther Clin Risk Manag. 2019-5-6

[6]
[Safety and efficacy of chimeric antigen receptor T cell in the treatment of elderly patients with hematological malignancies].

Zhonghua Xue Ye Xue Za Zhi. 2018-11-14

[7]
The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor- T cells immunotherapy in relapsed or refractory B-cell malignancies:a meta-analysis.

BMC Cancer. 2018-9-26

[8]
Molecular Approaches to Safe and Controlled Engineered T-cell Therapy.

Acta Naturae. 2018

[9]
[Progress in clinical studies of chimeric antigen receptor engineered T cells for treatment of childhood cancer].

Zhongguo Dang Dai Er Ke Za Zhi. 2017-11

[10]
Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis.

Immunotherapy. 2017-9

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