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CAR-T 治疗急性髓系白血病:障碍及如何克服

英文原题:CAR-T in the Treatment of Acute Myeloid Leukemia: Barriers and How to Overcome Them.

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CAR-T in the Treatment of Acute Myeloid Leukemia: Barriers and How to Overcome Them.

PubMed 2023/08/18(内容时间) Hemasphere Q1 · IF 11.3(JCR 2025)

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中文摘要

急性髓系白血病(AML)的传统治疗具有复发率高、毒性严重和总生存率差等特点。因此,开发新的治疗策略对于改善 AML 患者生存和生活质量至关重要。靶向 CD19 的嵌合抗原受体(CAR)T 细胞免疫疗法治疗 B 急性淋巴细胞白血病及多种成熟 B 细胞淋巴瘤已取得极大成功。然而,CAR-T 细胞疗法目前难以用于 AML,原因是缺乏类似 CD19 的髓系特异性靶点:目前已知的白血病原始细胞表面靶点也表达于健康造血干细胞、祖细胞及其后代细胞。此外,免疫抑制性肿瘤微环境会削弱 CAR-T 细胞的抗肿瘤活性。本文综述限制 CAR-T 治疗 AML 的临床挑战,并讨论克服这些障碍的有前景新策略。

展开英文摘要原文

Conventional therapies for acute myeloid leukemia (AML) are characterized by high rates of relapse, severe toxicities, and poor overall survival rates.

Thus, the development of new therapeutic strategies is crucial for improving the survival and quality of life of AML patients. CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy has been extremely successful in the treatment of B-cell acute lymphoid leukemia and several mature B-cell lymphomas.

However, the use of CAR T-cell therapy for AML is currently prevented due to the lack of a myeloid equivalent to CD19, as currently known cell surface targets on leukemic blasts are also expressed on healthy hematopoietic stem and progenitor cells as well as their progeny.

In addition, the immunosuppressive tumor microenvironment has a dampening effect on the antitumor activity of CAR-T cells.

Here, we review the therapeutic challenges limiting the use of CAR T-cell therapy for AML and discuss promising novel strategies to overcome them.

论文信息

作者
Vanhooren J、Dobbelaere R、Derpoorter C、Deneweth L、Van Camp L、Uyttebroeck A、De Moerloose B、Lammens T
单位
Department of Internal Medicine and Pediatrics, Ghent University, Belgium.Belgium
文献类型
综述
期刊
HemaSphere2023 Sep
原文标识
PubMed 37674860 · DOI 10.1097/HS9.0000000000000937