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突破屏障:通过微环境重塑增强实体瘤的 CAR 装甲 T 细胞治疗

英文原题:Breaking barriers: enhancing CAR-armored T cell therapy for solid tumors through microenvironment remodeling.

查看英文原题

Breaking barriers: enhancing CAR-armored T cell therapy for solid tumors through microenvironment remodeling.

PubMed 2025/09/03(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

近年来,嵌合抗原受体(CAR)T细胞疗法已成为治疗血液系统恶性肿瘤的革命性免疫疗法,但其治疗实体瘤的疗效仍面临多项挑战。本综述聚焦肿瘤微环境造成的障碍,这些障碍会妨碍工程化细胞有效迁移、浸润和精准靶向肿瘤。我们讨论肿瘤微环境如何构成细胞疗法必须克服的物理屏障,并介绍设计新型CAR-T 细胞疗法的持续努力,以提高肿瘤靶向精准度、改善稳定性及克服靶向肿瘤同时损伤正常组织的毒性。我们重点关注临床和临床前研究的近期进展,这些研究旨在重编程免疫抑制性肿瘤微环境,包括基质和血管正常化策略,从而提高工程化治疗细胞在免疫肿瘤学应用中的肿瘤归巢和靶向能力。随着CAR设计创新持续推进,个体化细胞疗法领域正进入令人振奋的新时代,为难治性实体瘤患者带来新的希望。

展开英文摘要原文

Whilst chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary immunotherapeutic approach for hematological malignancies in recent years, several challenges remain to potentiate the efficacy of CAR T cell therapies for solid tumors.

Here, we focus on the obstacles posed by the tumor microenvironment that hinder the effective trafficking, infiltration and precise tumor targeting by engineered cells.

We discuss how the tumor microenvironment presents a physical barrier that needs to be surpassed for effective cell therapies and ongoing efforts in designing innovative CAR T cell therapies with enhanced tumor-targeting precision, improved stability, and overcoming on-target off-tumor toxicity are presented.

We focus on recent advances in clinical and preclinical settings to reprogram the immunosuppressive tumor microenvironment, including stroma and blood vessel normalization strategies that can be leveraged to improve the tumor-homing and tumor-targeting potential of engineered therapeutic cells for immuno-oncology applications. As the endeavors for innovative CAR designs continue, we are entering an exciting era in the field of personalized cell therapies offering renewed hope to patients with hard-to-treat solid tumors.

论文信息

作者
Andreou T、Neophytou C、Kalli M、Mpekris F、Stylianopoulos T
单位
Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.Italy
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 40969762 · DOI 10.3389/fimmu.2025.1638186