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重塑未来:以合成生物学、工程学和经济学洞见弥合 CAR-T 细胞疗法的差距

英文原题:ReCARving the future: bridging CAR T-cell therapy gaps with synthetic biology, engineering, and economic insights.

查看英文原题

ReCARving the future: bridging CAR T-cell therapy gaps with synthetic biology, engineering, and economic insights.

PubMed 2024/09/05(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法已经彻底改变了血液系统恶性肿瘤的治疗,在原本难治的病症中提供了显著的缓解率。然而,其向更广泛肿瘤学应用的扩展面临重大障碍,包括在实体瘤中的疗效有限、与毒性相关的安全性担忧,以及制造和可扩展性方面的物流挑战。本综述批判性地审视了旨在克服这些障碍的最新进展,重点介绍了CAR-T 细胞工程、新型抗原靶向策略以及肿瘤微环境内递送和持久性改善方面的创新。我们还讨论了作为现货型疗法的异体CAR-T 细胞的开发、减轻不良反应的策略,以及CAR-T 细胞与其他治疗方式的整合。这一综合分析强调了这些策略在提高CAR-T 细胞疗法的安全性、疗效和可及性方面的协同潜力,并为其在癌症治疗中的演进轨迹提供了前瞻性视角。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions.

However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment.

We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and the integration of CAR T cells with other therapeutic modalities. This comprehensive analysis underscores the synergistic potential of these strategies to enhance the safety, efficacy, and accessibility of CAR T-cell therapies, providing a forward-looking perspective on their evolutionary trajectory in cancer treatment.

论文信息

作者
Ali A、DiPersio JF
第一作者单位
Stem Cell Transplant and Cellular Immunotherapy Program, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, United States.United States
通讯作者单位
Center for Gene and Cellular Immunotherapy, Washington University in Saint Louis, Saint Louis, MO, United States.United States
文献类型
综述
期刊
Frontiers in immunology2024
原文标识
PubMed 39301026 · DOI 10.3389/fimmu.2024.1432799