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基于 CAR-T 治疗的创新:增强当代抗肿瘤治疗

英文原题:CAR-T therapy-based innovations in the enhancement of contemporary anti-tumor therapies.

查看英文原题

CAR-T therapy-based innovations in the enhancement of contemporary anti-tumor therapies.

PubMed 2025/07/02(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

CAR-T(CAR-T)细胞疗法已经彻底改变了血液系统恶性肿瘤的治疗格局;然而,由于抗原异质性、抑制性肿瘤微环境以及肿瘤内在耐药机制,其在实体瘤中的疗效仍然有限。与此同时,免疫检查点阻断(ICB)疗法已取得临床里程碑式进展,但常因抗原呈递受损、干扰素信号失调和免疫排斥而失败。CAR-T 疗法相关技术的最新进展,包括多特异性和装甲化CAR构建体、基因编辑策略以及合成回路,为克服这些障碍并扩大治疗疗效提供了新的机会。人工智能(AI)进一步加速了新型肿瘤抗原的发现、优化了CAR设计,并实现了治疗反应的实时建模。将CAR-T 疗法与AI驱动平台、代谢重编程、双特异性抗体以及先进单细胞分析相结合,代表了一种增强肿瘤靶向性和应答持久性的强有力策略。本综述总结了新兴的CAR-T 疗法创新,探讨了其与免疫疗法的协同应用,并讨论了当前在安全性、生产制造、成本和生物标志物验证方面相关的挑战。这些多学科努力共同为更有效和个性化的癌症治疗铺平了道路。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment landscape for hematologic malignancies; however, its efficacy in solid tumors remains limited due to antigen heterogeneity, a suppressive tumor microenvironment, and tumor-intrinsic resistance mechanisms. In parallel, immune checkpoint blockade (ICB) therapies have achieved clinical milestones but often fail due to impaired antigen presentation, interferon signaling dysregulation, and immune exclusion. Recent advances in CAR-T therapy-based technologies including multi-specific and armored CAR constructs, gene-editing strategies, and synthetic circuits offer new opportunities to overcome these barriers and expand therapeutic efficacy.

Artificial intelligence (AI) has further accelerated the discovery of novel tumor antigens, optimized CAR design, and enabled real-time modeling of treatment responses. Integration of CAR-T therapy with AI-driven platforms, metabolic reprogramming, bispecific antibodies, and advanced single-cell analytics represents a powerful strategy to enhance tumor targeting and durability of response.

This review summarizes emerging CAR-T therapy-based innovations, explores their synergistic applications with immunotherapies, and discusses current challenges related to safety, manufacturing, cost, and biomarker validation. These multidisciplinary efforts collectively pave the way toward more effective and personalized cancer treatment.

论文信息

作者
Zhang WY、Yang LY、Fan XX
单位
Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, School of Chinese Medicine, Macau University of Science and Technology, Macau, Macau SAR, China.China
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 40672956 · DOI 10.3389/fimmu.2025.1622433