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克服当前缺陷的新一代 CAR-T 细胞

英文原题:Next-generation CAR T cells to overcome current drawbacks.

查看英文原题

Next-generation CAR T cells to overcome current drawbacks.

PubMed 2020/06/27(内容时间) Int J Hematol Q3 · IF 1.9(JCR 2025)

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中文摘要

作为肿瘤领域迅速发展的治疗方式,自体基因修饰嵌合抗原受体(CAR)T 细胞过继转移已显示出显著疗效,并可治愈部分复发/难治性血液系统恶性肿瘤患者。这种使用“活体药物”的治疗模式,为剩余治疗选择可能有限的癌症患者带来了许多令人期待的新型治疗策略。尽管 CAR-T 细胞治疗血液系统恶性肿瘤早期取得成功,其广泛应用仍面临诸多障碍,包括细胞制备能力受限、T 细胞基线质量不佳、输注后不良事件(如细胞因子释放综合征(CRS)和神经毒性),以及宿主对非人源 CAR 的排斥。此外,不同血液系统疾病各有独特的复发机制,未来临床试验必须解决这些机制,才能进一步提高 CAR-T 治疗的疗效。本综述将按疾病类型介绍当前阻碍 CAR-T 细胞治疗血液系统恶性肿瘤疗效的因素,并回顾旨在增强 CAR-T 细胞效力和适用范围的近期创新,最终希望为将这类疗法纳入血液肿瘤标准医疗管理建立框架。

展开英文摘要原文

As a rapidly emerging treatment in the oncology field, adoptive transfer of autologous, genetically modified chimeric antigen receptor (CAR) T cells has shown striking efficacy and is curative in certain relapsed/refractory patients with hematologic malignancy. This treatment modality of using a "living drug" offers many tantalizing and novel therapeutic strategies for cancer patients whose remaining treatment options may have otherwise been limited.

Despite the early success of CAR T cells in hematologic malignancies, many barriers remain for widespread adoption. General barriers include cellular manufacturing limitations, baseline quality of the T cells, adverse events post-infusion such as cytokine release syndrome (CRS) and neurotoxicity, and host rejection of non-human CARs.

Additionally, each hematologic disease presents unique mechanisms of relapse which have to be addressed in future clinical trials if we are to augment the efficacy of CAR T treatment.

In this review, we will describe current barriers to hindering efficacy of CAR T-cell treatment for hematologic malignancies in a disease-specific manner and review recent innovations aimed at enhancing the potency and applicability of CAR T cells, with the overall goal of building a framework to begin incorporating this form of therapy into the standard medical management of blood cancers.

论文信息

作者
Lundh S、Maji S、Melenhorst JJ
第一作者单位
Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.United States
通讯作者单位
Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. mej@pennmedicine.upenn.edu.United States
文献类型
综述
期刊
International journal of hematology2021 Nov
原文标识
PubMed 32594314 · DOI 10.1007/s12185-020-02923-9