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装甲嵌合抗原受体T细胞:T细胞癌症免疫疗法的新篇章。

Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy.

作者信息

Hawkins Elizabeth R, D'Souza Reena R, Klampatsa Astero

机构信息

Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.

出版信息

Biologics. 2021 Apr 14;15:95-105. doi: 10.2147/BTT.S291768. eCollection 2021.


DOI:10.2147/BTT.S291768
PMID:33883875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8053711/
Abstract

Chimeric antigen receptor (CAR) T-cell therapy engineers T-cells to express a synthetic receptor which redirects effector function to the tumor, to improve efficacy and reduce toxicities associated with conventional treatments, such as radiotherapy and chemotherapy. This approach has proved effective in treating hematological malignancies; however, the same effects have not been observed in solid tumors. The immunosuppressive tumor microenvironment (TME) creates a significant barrier to solid tumor efficacy and reduces the anti-cancer activity of endogenous tumor-resident immune cells, enabling cancer progression. In recent years, researchers have attempted to enhance CAR T-cell function in the TME by engineering the cells to express various proteins alongside the CAR. Examples of this engineering include inducing CAR T-cells to secrete cytokines or express cytokine receptors to modulate the cytokine milieu of the TME. Alternatively, the CAR T-cell may secrete antibody-like proteins to target a range of tumor antigens. Collectively, these methods are termed armored CAR T-cell therapy, and in this review, we will discuss the range of armored CAR T-cell approaches which have been investigated to date.

摘要

嵌合抗原受体(CAR)T细胞疗法通过对T细胞进行工程改造,使其表达一种合成受体,该受体将效应功能重定向至肿瘤,以提高疗效并降低与放疗和化疗等传统治疗相关的毒性。这种方法已被证明在治疗血液系统恶性肿瘤方面有效;然而,在实体瘤中尚未观察到相同的效果。免疫抑制性肿瘤微环境(TME)对实体瘤疗效构成了重大障碍,并降低了内源性肿瘤驻留免疫细胞的抗癌活性,从而使癌症进展。近年来,研究人员试图通过对细胞进行工程改造,使其在表达CAR的同时表达各种蛋白质,来增强TME中CAR T细胞的功能。这种工程改造的例子包括诱导CAR T细胞分泌细胞因子或表达细胞因子受体,以调节TME的细胞因子环境。或者,CAR T细胞可以分泌抗体样蛋白来靶向一系列肿瘤抗原。总的来说,这些方法被称为武装CAR T细胞疗法,在本综述中,我们将讨论迄今为止已研究的一系列武装CAR T细胞方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e73/8053711/2acc499f9f68/BTT-15-95-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e73/8053711/07e1cdfbeb83/BTT-15-95-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e73/8053711/2acc499f9f68/BTT-15-95-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e73/8053711/07e1cdfbeb83/BTT-15-95-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e73/8053711/2acc499f9f68/BTT-15-95-g0002.jpg

相似文献

[1]
Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy.

Biologics. 2021-4-14

[2]
Befriending the Hostile Tumor Microenvironment in CAR T-Cell Therapy.

Front Immunol. 2020

[3]
CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment.

Front Immunol. 2019-2-5

[4]
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Exp Hematol Oncol. 2024-9-30

[5]
Armored TGFβRIIDN ROR1-CAR T cells reject solid tumors and resist suppression by constitutively-expressed and treatment-induced TGFβ1.

J Immunother Cancer. 2024-4-12

[6]
Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy.

Biochem Soc Trans. 2016-4-15

[7]
Chimeric antigen receptor-engineered T-cell therapy for liver cancer.

Hepatobiliary Pancreat Dis Int. 2018-5-24

[8]
Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures.

Cancers (Basel). 2023-12-20

[9]
Target selection of CAR T cell therapy in accordance with the TME for solid tumors.

Am J Cancer Res. 2019-2-1

[10]
Gene modification strategies for next-generation CAR T cells against solid cancers.

J Hematol Oncol. 2020-5-18

引用本文的文献

[1]
CAR-T cell therapy in brain malignancies: obstacles in the face of cellular trafficking and persistence.

Front Immunol. 2025-6-19

[2]
Membrane-bound IL-15 co-expression powers a potent and persistent CD70-targeted TRuC T-cell therapy.

Front Immunol. 2025-5-30

[3]
Identification of M2 macrophage-related genes associated with diffuse large B-cell lymphoma via bioinformatics and machine learning approaches.

Biol Direct. 2025-4-29

[4]
Engineering resilient CAR T cells for immunosuppressive environment.

Mol Ther. 2025-6-4

[5]
Orthogonalized human protease control of secreted signals.

Nat Chem Biol. 2025-1-15

[6]
Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer.

Cancer Immunol Immunother. 2025-1-3

[7]
Armoring chimeric antigen receptor (CAR) T cells as micropharmacies for cancer therapy.

Immunooncol Technol. 2024-9-25

[8]
Chimeric antigen receptor T-cell therapy in autoimmune diseases.

Front Immunol. 2024-11-19

[9]
Significant Advancements and Evolutions in Chimeric Antigen Receptor Design.

Int J Mol Sci. 2024-11-13

[10]
Orthogonalized human protease control of secreted signals.

bioRxiv. 2024-10-21

本文引用的文献

[1]
EGLIF-CAR-T Cells Secreting PD-1 Blocking Antibodies Significantly Mediate the Elimination of Gastric Cancer.

Cancer Manag Res. 2020-9-23

[2]
Augmenting the Effectiveness of CAR-T Cells by Enhanced Self-Delivery of PD-1-Neutralizing scFv.

Front Cell Dev Biol. 2020-8-18

[3]
Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics.

Front Oncol. 2020-7-23

[4]
Prognostic Significance of Tumor-Infiltrating Natural Killer Cells in Solid Tumors: A Systematic Review and Meta-Analysis.

Front Immunol. 2020

[5]
CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape.

Front Immunol. 2020

[6]
Prognostic Values of Transforming Growth Factor-Beta Subtypes in Ovarian Cancer.

Biomed Res Int. 2020

[7]
Third-generation anti-CD19 chimeric antigen receptor T-cells incorporating a TLR2 domain for relapsed or refractory B-cell lymphoma: a phase I clinical trial protocol (ENABLE).

BMJ Open. 2020-2-9

[8]
Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments.

Cancer Immunol Res. 2020-2-4

[9]
Immune checkpoint inhibitors: a narrative review of considerations for the anaesthesiologist.

Br J Anaesth. 2020-1-29

[10]
Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin's Lymphoma.

Mol Ther Oncolytics. 2019-8-28

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