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分子靶向药物联合 CAR-T 细胞治疗血液系统恶性肿瘤的研究进展

英文原题:Advances in molecular targeted drugs in combination with CAR-T cell therapy for hematologic malignancies.

查看英文原题

Advances in molecular targeted drugs in combination with CAR-T cell therapy for hematologic malignancies.

PubMed 2024/03/26(内容时间) Drug Resist Updat Q1 · IF 22(JCR 2025)

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中文摘要

分子靶向药物和嵌合抗原受体(CAR)T细胞疗法均属于特异性生物治疗,已显著提高血液系统恶性肿瘤的治疗效果。然而,两者仍面临治疗耐药和治疗后复发等挑战。分子靶向药物与CAR-T 细胞联合使用,可能调节免疫、改善肿瘤微环境(TME)、促进细胞凋亡并提高肿瘤细胞对杀伤的敏感性。这种方法有望对癌细胞形成双重协同攻击,有效清除微小残留病灶并克服治疗耐药。此外,分子靶向药物还可通过诱导肿瘤靶抗原表达、逆转CAR-T 细胞耗竭以及减轻CAR-T 相关毒性,直接或间接增强CAR-T 的抗肿瘤作用。因此,分子靶向药物联合CAR-T 是治疗血液系统恶性肿瘤的一种有前景的新策略。本文重点分析CAR-T 治疗耐药的机制及其逆转方式,并综述CAR-T 联合分子靶向药物的协同机制、安全性和未来挑战。我们希望探讨这种联合疗法对血液系统恶性肿瘤患者的潜在获益,并为后续临床研究提供依据。

展开英文摘要原文

Molecular targeted drugs and chimeric antigen receptor (CAR) T cell therapy represent specific biological treatments that have significantly improved the efficacy of treating hematologic malignancies.

However, they face challenges such as drug resistance and recurrence after treatment. Combining molecular targeted drugs and CAR-T cells could regulate immunity, improve tumor microenvironment (TME), promote cell apoptosis, and enhance sensitivity to tumor cell killing. This approach might provide a dual coordinated attack on cancer cells, effectively eliminating minimal residual disease and overcoming therapy resistance.

Moreover, molecular targeted drugs can directly or indirectly enhance the anti-tumor effect of CAR-T cells by inducing tumor target antigen expression, reversing CAR-T cell exhaustion, and reducing CAR-T cell associated toxic side effects.

Therefore, combining molecular targeted drugs with CAR-T cells is a promising and novel tactic for treating hematologic malignancies. In this review article, we focus on analyzing the mechanism of therapy resistance and its reversal of CAR-T cell therapy resistance, as well as the synergistic mechanism, safety, and future challenges in CAR-T cell therapy in combination with molecular targeted drugs.

We aim to explore the benefits of this combination therapy for patients with hematologic malignancies and provide a rationale for subsequent clinical studies.

论文信息

作者
Huang Y、Qin Y、He Y、Qiu D、Zheng Y、Wei J、Zhang L、Yang DH
第一作者单位
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China. Electronic address: hyx6610@163.com.China
通讯作者单位
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China. Electronic address: liyuhua2011gz@163.com.China
文献类型
综述 · 非美国政府资助研究
期刊
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy2024 May
原文标识
PubMed 38569225 · DOI 10.1016/j.drup.2024.101082