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治疗 AML 的新兴 CAR-T 细胞策略

英文原题:Emerging CAR T Cell Strategies for the Treatment of AML.

查看英文原题

Emerging CAR T Cell Strategies for the Treatment of AML.

PubMed 2022/02/27(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

在其细胞表面表达嵌合抗原受体(CAR)的工程化T细胞可以重定向抗原特异性。这一能力使CAR成为最有前景的癌症治疗药物之一。用于治疗B细胞血液系统恶性肿瘤患者的CAR-T 细胞已显示出令人瞩目的结果。临床表现已产生多项试验,迄今为止已有五种CAR-T 细胞疗法获得美国食品药品监督管理局(FDA)批准。

然而,新出现的临床数据和近期发现已识别出CAR-T 细胞疗法引起的一些免疫相关毒性。鉴于其疗效以及同一概念验证的应用,有必要在其他血液系统恶性肿瘤(如白血病)中开展进一步研究。本综述讨论了CAR-T 细胞疗法在临床前和人体经验中的既往发现。

此外,我们描述了过继性免疫治疗新靶点的近期进展。在此,我们介绍了通过基因工程、基因编辑、细胞编程和合成生物学形式的进步进行CAR-T 细胞改造的临床前研究的一些早期发现,以及通过表观遗传重塑恢复耗竭CAR-T 细胞功能的持续努力。我们旨在阐明聚焦于急性髓系白血病(AML)的新靶点。

展开英文摘要原文

Engineered T cells expressing chimeric antigen receptors (CARs) on their cell surface can redirect antigen specificity. This ability makes CARs one of the most promising cancer therapeutic agents. CAR-T cells for treating patients with B cell hematological malignancies have shown impressive results. Clinical manifestation has yielded several trials, so far five CAR-T cell therapies have received US Food and Drug Administration (FDA) approval.

However, emerging clinical data and recent findings have identified some immune-related toxicities due to CAR-T cell therapy. Given the outcome and utilization of the same proof of concept, further investigation in other hematological malignancies, such as leukemias, is warranted. This review discusses the previous findings from the pre-clinical and human experience with CAR-T cell therapy.

Additionally, we describe recent developments of novel targets for adoptive immunotherapy.

Here we present some of the early findings from the pre-clinical studies of CAR-T cell modification through advances in genetic engineering, gene editing, cellular programming, and formats of synthetic biology, along with the ongoing efforts to restore the function of exhausted CAR-T cells through epigenetic remodeling.

We aim to shed light on the new targets focusing on acute myeloid leukemia (AML).

论文信息

作者
Vishwasrao P、Li G、Boucher JC、Smith DL、Hui SK
单位
Department of Radiation Oncology, City of Hope Medical Center, Duarte, CA 91010, USA.United States
文献类型
综述
期刊
Cancers2022 Feb 27
原文标识
PubMed 35267549 · DOI 10.3390/cancers14051241