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双靶点 CAR-T 细胞疗法:改善血液系统恶性肿瘤治疗效果的新策略

英文原题:Dual-target CAR-T cell therapy: A new strategy to improve the therapeutic effect of hematological malignancies.

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Dual-target CAR-T cell therapy: A new strategy to improve the therapeutic effect of hematological malignancies.

PubMed 2025/07/01(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

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中文摘要

CAR-T(CAR-T)细胞疗法代表了肿瘤免疫治疗的重大进展,在血液系统恶性肿瘤的治疗中展现出显著疗效。然而,单靶点CAR-T 疗法面临若干挑战,包括抗原逃逸、on-target off-tumor毒性以及肿瘤异质性。为解决这些局限性,双靶点CAR-T 细胞疗法应运而生。通过识别两种肿瘤抗原,双靶点CAR-T 疗法拓宽了CAR-T 细胞的抗原识别谱,并大幅降低了抗原逃逸的风险。此外,逻辑门控设计的引入增强了其精确性并最大限度地减少了on-target off-tumor毒性。本综述全面分析了多种双靶点CAR-T 细胞类型,包括序贯CAR-T 细胞、双信号CAR、串联CAR、AND门CAR和抑制性CAR,重点关注其在血液系统恶性肿瘤中的应用及治疗疗效。此外,本综述深入探讨了双靶点CAR-T 细胞疗法的独特优势、当前研究进展及面临的挑战。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cell therapy represents a significant advancement in tumor immunotherapy, demonstrating notable efficacy in the treatment of hematological malignancies. Nevertheless, single-target CAR-T therapy encounters several challenges, including antigen escape, on-target off-tumor toxicity, and tumor heterogeneity.

To address these limitations, dual-target CAR-T cell therapy has been developed. By recognizing two tumor antigens, dual-target CAR-T therapy broadens the antigen recognition spectrum of CAR-T cells and substantially mitigates the risk of antigen escape.

Additionally, the incorporation of logic gate control design enhances its precision and minimizes on-target off-tumor toxicity. This review provides a comprehensive analysis of various dual-target CAR-T cell types, including sequential CAR-T cells, dual-signal CARs, tandem CARs, AND-gate CARs, and inhibitory CARs, with a focus on their applications and therapeutic efficacy in hematological malignancies.

Furthermore, this review provides an in-depth examination of the unique advantages, current research progress, and challenges associated with dual-target CAR-T cell therapy.

论文信息

作者
Wang S、Li X、Ning H、Wu Y
第一作者单位
Senior Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, 100 West Fourth Ring Road, Fengtai District, Beijing 100071, PR China.China
通讯作者单位
Senior Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, 100 West Fourth Ring Road, Fengtai District, Beijing 100071, PR China. Electronic address: rippleya@126.com.China
文献类型
综述
期刊
Critical reviews in oncology/hematology2025 Oct
原文标识
PubMed 40609918 · DOI 10.1016/j.critrevonc.2025.104824