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重塑未来:利用合成生物学、工程学和经济学的洞见,弥合 CAR T 细胞治疗的差距。

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

机构信息

Stem Cell Transplant and Cellular Immunotherapy Program, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, United States.

Center for Gene and Cellular Immunotherapy, Washington University in Saint Louis, Saint Louis, MO, United States.

出版信息

Front Immunol. 2024 Sep 5;15:1432799. doi: 10.3389/fimmu.2024.1432799. eCollection 2024.

Abstract

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.

摘要

嵌合抗原受体 (CAR) T 细胞疗法彻底改变了血液系统恶性肿瘤的治疗方式,为原本难治的疾病提供了显著的缓解率。然而,要将其拓展到更广泛的肿瘤学应用中,仍面临着重大障碍,包括在实体瘤中的疗效有限、与毒性相关的安全性问题,以及在制造和可扩展性方面的后勤挑战。本综述批判性地评估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在肿瘤微环境中传递和持久性方面的改进。我们还讨论了同种异体 CAR T 细胞作为现成疗法的发展、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。这项全面分析强调了这些策略的协同潜力,以提高 CAR T 细胞疗法的安全性、疗效和可及性,为其在癌症治疗中的发展轨迹提供了前瞻性视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b9/11410633/99b29a550740/fimmu-15-1432799-g001.jpg

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