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工程化 T 细胞治疗癌症的未来展望。

Future perspectives on engineered T cells for cancer.

机构信息

Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy at the University of Pennsylvania, Philadelphia, PA, USA; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.

Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Trends Cancer. 2024 Aug;10(8):687-695. doi: 10.1016/j.trecan.2024.05.007. Epub 2024 Jun 8.


DOI:10.1016/j.trecan.2024.05.007
PMID:38853073
Abstract

Chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary treatment for hematological malignancies, but its adaptation to solid tumors is impeded by multiple challenges, particularly T cell dysfunction and exhaustion. The heterogeneity and inhospitableness of the solid tumor microenvironment (TME) contribute to diminished CAR T cell efficacy exhibited by reduced cytotoxicity, proliferation, cytokine secretion, and the upregulation of inhibitory receptors, similar to the phenotype of tumor-infiltrating lymphocytes (TILs). In this review, we highlight recent advances in T cell therapy for solid tumors, particularly brain cancer. Innovative strategies, including locoregional delivery and 'armoring' CAR T cells with cytokines such as interleukin (IL)-18, are under investigation to improve efficacy and safety. We also highlight emerging issues with toxicity management of CAR T cell adverse events. This review discusses the obstacles associated with CAR T cell therapy in the context of solid tumors and outlines current and future strategies to overcome these challenges.

摘要

嵌合抗原受体 (CAR) T 细胞疗法已成为血液恶性肿瘤的一种革命性治疗方法,但由于多种挑战,包括 T 细胞功能障碍和衰竭,其在实体瘤中的应用受到阻碍。实体瘤微环境 (TME) 的异质性和不适合性导致 CAR T 细胞的功效降低,表现为细胞毒性、增殖、细胞因子分泌和抑制性受体的上调减少,类似于肿瘤浸润淋巴细胞 (TILs) 的表型。在这篇综述中,我们重点介绍了用于实体瘤,特别是脑癌的 T 细胞治疗的最新进展。正在研究创新策略,包括局部递送和用白细胞介素 (IL)-18 等细胞因子“武装”CAR T 细胞,以提高疗效和安全性。我们还强调了 CAR T 细胞不良事件毒性管理方面的新问题。这篇综述讨论了与实体瘤中 CAR T 细胞治疗相关的障碍,并概述了克服这些挑战的当前和未来策略。

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Future perspectives on engineered T cells for cancer.

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引用本文的文献

[1]
Can We Use CAR-T Cells to Overcome Immunosuppression in Solid Tumours?

Biology (Basel). 2025-8-12

[2]
Constructing the cure: engineering the next wave of antibody and cellular immune therapies.

J Immunother Cancer. 2025-8-25

[3]
IL-7 armed binary CAR T cell strategy to augment potency against solid tumors.

Front Immunol. 2025-7-30

[4]
Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.

JHEP Rep. 2025-4-11

[5]
Emerging Concepts in Immuno-Oncology: Insights from Natural Language Processing-Driven Co-Occurrence Analysis.

ACS Omega. 2025-6-27

[6]
IL-7 armed binary CAR T cell strategy to augment potency against solid tumors.

bioRxiv. 2025-6-27

[7]
Chimeric Antigen Receptor (CAR) T Cells Releasing Soluble SLAMF6 Isoform 2 Gain Superior Anti-Cancer Cell Functionality in an Auto-Stimulatory Fashion.

Cells. 2025-6-14

[8]
Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.

Acta Neuropathol Commun. 2025-6-5

[9]
Onboard, tethered IL-12 boosts potency of the Tmod NOT gate and preserves selectivity.

J Immunother Cancer. 2025-5-21

[10]
T Lymphocyte Integrated Endoplasmic Reticulum Ca Store Signaling Functions Are Linked to Sarco/Endoplasmic Reticulum Ca-ATPase Isoform-Specific Levels of Regulation.

Int J Mol Sci. 2025-4-27

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