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嵌合抗原受体 T 细胞：漫漫实体瘤征途。

CAR-T cells: the long and winding road to solid tumors.

机构信息

Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

出版信息

Cell Death Dis. 2018 Feb 15;9(3):282. doi: 10.1038/s41419-018-0278-6.

DOI:10.1038/s41419-018-0278-6
PMID:29449531
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5833816/
Abstract

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles.

摘要

采用重编程 T 细胞的实体瘤过继细胞疗法可以被视为癌症标志的“下一代”。CAR-T 细胞在实体肿瘤中的疗效不如在液体肿瘤中那么有效，因为它们无法到达和在肿瘤病灶周围的微环境中存活。肿瘤成分、基质和免疫细胞之间发生的错综复杂的交叉相互作用网络导致无效的无能状态，有利于逃避宿主的防御。我们的目标是在此追踪实体肿瘤对 CAR-T 细胞施加的影响，强调可能需要开发和完善的陷阱和策略，以克服这些障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/0654065a3d2c/41419_2018_278_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/26e4a0d346b5/41419_2018_278_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/5d4ab595e841/41419_2018_278_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/5a082d4391cc/41419_2018_278_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/cf14c42dd64d/41419_2018_278_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/0654065a3d2c/41419_2018_278_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/26e4a0d346b5/41419_2018_278_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/5d4ab595e841/41419_2018_278_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/5a082d4391cc/41419_2018_278_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/cf14c42dd64d/41419_2018_278_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3053/5833816/0654065a3d2c/41419_2018_278_Fig5_HTML.jpg

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CAR-T cells: the long and winding road to solid tumors.

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引用本文的文献

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Mechanisms and clinical advancements of cell-based immunotherapies in non-small cell lung cancer: an integrated perspective.

Front Immunol. 2025-8-19

[2]
Adoptive T-Cell Therapy in Sarcomas.

Curr Oncol Rep. 2025-8-14

[3]
Emerging CAR immunotherapies: broadening therapeutic horizons beyond cancer.

Clin Exp Med. 2025-8-4

[4]
Spatiotemporal dynamics of tumor-CAR T-cell interaction following local administration in solid cancers.

PLoS Comput Biol. 2025-6-3

[5]
Comprehensive advances in HER2-positive and HER2-negative breast cancer: unveiling molecular mechanisms and exploring cutting-edge targeted therapies for enhanced patient outcomes.

Naunyn Schmiedebergs Arch Pharmacol. 2025-5-29

[6]
Engaging T cells for cleanup.

Front Immunol. 2025-5-6

[7]
The Combination of Oncolytic Virus and Antibody Blockade of TGF-β Enhances the Efficacy of αvβ6-Targeting CAR T Cells Against Pancreatic Cancer in an Immunocompetent Model.

Cancers (Basel). 2025-4-30

[8]
Cell-based immunotherapies for solid tumors: advances, challenges, and future directions.

Front Oncol. 2025-4-28

[9]
Strategies for Altering Delivery Technologies to Optimize CAR Therapy.

Int J Mol Sci. 2025-3-30

[10]
Use of a universal targeting CAR T cell to simultaneously kill cancer cells and cancer-associated fibroblasts.

Front Immunol. 2025-2-17

本文引用的文献

[1]
High-Affinity GD2-Specific CAR T Cells Induce Fatal Encephalitis in a Preclinical Neuroblastoma Model.

Cancer Immunol Res. 2017-11-27

[2]
CAR T Cells Administered in Combination with Lymphodepletion and PD-1 Inhibition to Patients with Neuroblastoma.

Mol Ther. 2017-6-9

[3]
[CAR T-cell therapy: Balance of efficacy and safety].

Mol Biol (Mosk). 2017

[4]
Hallmarks of response to immune checkpoint blockade.

Br J Cancer. 2017-6-27

[5]
Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA Metastatic Colorectal Cancers.

Mol Ther. 2017-5-3

[6]
Possible Compartmental Cytokine Release Syndrome in a Patient With Recurrent Ovarian Cancer After Treatment With Mesothelin-targeted CAR-T Cells.

J Immunother. 2017-4

[7]
New development in CAR-T cell therapy.

J Hematol Oncol. 2017-2-21

[8]
Improving Chimeric Antigen Receptor-Modified T Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer.

Mol Ther. 2017-1-4

[9]
Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma.

J Hematol Oncol. 2017-1-5

[10]
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

N Engl J Med. 2016-12-29

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