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嵌合抗原受体T细胞效力:从结构元件到载体骨架组件

CAR-T cell potency: from structural elements to vector backbone components.

作者信息

Mazinani Marzieh, Rahbarizadeh Fatemeh

机构信息

Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-111, Tehran, Iran.

Research and Development Center of Biotechnology, Tarbiat Modares University, Tehran, Iran.

出版信息

Biomark Res. 2022 Sep 19;10(1):70. doi: 10.1186/s40364-022-00417-w.


DOI:10.1186/s40364-022-00417-w
PMID:36123710
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9487061/
Abstract

Chimeric antigen receptor (CAR) T cell therapy, in which a patient's own T lymphocytes are engineered to recognize and kill cancer cells, has achieved remarkable success in some hematological malignancies in preclinical and clinical trials, resulting in six FDA-approved CAR-T products currently available in the market. Once equipped with a CAR construct, T cells act as living drugs and recognize and eliminate the target tumor cells in an MHC-independent manner. In this review, we first described all structural modular of CAR in detail, focusing on more recent findings. We then pointed out behind-the-scene elements contributing to CAR expression and reviewed how CAR expression can be drastically affected by the elements embedded in the viral vector backbone.

摘要

嵌合抗原受体(CAR)T细胞疗法是指对患者自身的T淋巴细胞进行改造,使其能够识别并杀死癌细胞。在临床前和临床试验中,该疗法已在一些血液系统恶性肿瘤中取得了显著成功,目前市场上已有六种获得美国食品药品监督管理局(FDA)批准的CAR-T产品。一旦配备了CAR构建体,T细胞就会充当生物药物,并以不依赖主要组织相容性复合体(MHC)的方式识别和消除靶肿瘤细胞。在这篇综述中,我们首先详细描述了CAR的所有结构模块,重点关注了最新研究结果。然后,我们指出了影响CAR表达的潜在因素,并探讨了病毒载体骨架中所含元件如何对CAR表达产生重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/ee842d09c281/40364_2022_417_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/d0720da9dea1/40364_2022_417_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/1031108c4f59/40364_2022_417_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/ebe571b95877/40364_2022_417_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/89cfcfef4e05/40364_2022_417_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/11d0e097a0bf/40364_2022_417_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/33ba9b3cf831/40364_2022_417_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/ee842d09c281/40364_2022_417_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/d0720da9dea1/40364_2022_417_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/1031108c4f59/40364_2022_417_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/ebe571b95877/40364_2022_417_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/89cfcfef4e05/40364_2022_417_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/11d0e097a0bf/40364_2022_417_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/33ba9b3cf831/40364_2022_417_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9688/9487061/ee842d09c281/40364_2022_417_Fig7_HTML.jpg

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CAR-T cell potency: from structural elements to vector backbone components.

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引用本文的文献

[1]
CAR-T cell therapy for glioblastoma: advances, challenges, and future directions.

Ann Med Surg (Lond). 2025-7-18

[2]
Challenges in the preclinical design and assessment of CAR-T cells.

Front Immunol. 2025-8-8

[3]
Optimised modular anti-FLAG CAR T cells for solid tumor therapy.

Clin Transl Immunology. 2025-8-21

[4]
Tracing the development of CAR-T cell design: from concept to next-generation platforms.

Front Immunol. 2025-7-17

[5]
Emerging CAR immunotherapies: broadening therapeutic horizons beyond cancer.

Clin Exp Med. 2025-8-4

[6]
Future perspectives on novel CAR-T therapeutics beyond CD19 and BCMA in onco-hematology.

Front Immunol. 2025-7-14

[7]
CAR-iNKT cells: redefining the frontiers of cellular immunotherapy.

Front Immunol. 2025-7-11

[8]
Discordant CAR-T cell signaling: implications of divergence from physiological T cell activation.

J Transl Med. 2025-7-25

[9]
Cell-Based Therapies for Solid Tumors: Challenges and Advances.

Int J Mol Sci. 2025-6-9

[10]
Neurological complications associated with chimeric antigen receptor T cell therapy.

J Cereb Blood Flow Metab. 2025-5-2

本文引用的文献

[1]
Current Status and Perspectives of Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Hematological Malignancies.

Cancers (Basel). 2022-6-30

[2]
Universal allogeneic CAR T cells engineered with Sleeping Beauty transposons and CRISPR-CAS9 for cancer immunotherapy.

Mol Ther. 2022-10-5

[3]
Low-affinity CAR T cells exhibit reduced trogocytosis, preventing rapid antigen loss, and increasing CAR T cell expansion.

Leukemia. 2022-7

[4]
Special Chimeric Antigen Receptor (CAR) Modifications of T Cells: A Review.

Front Oncol. 2022-3-22

[5]
Development of a Novel Anti-CD19 CAR Containing a Fully Human scFv and Three Costimulatory Domains.

Front Oncol. 2022-1-18

[6]
The Implementation of TNFRSF Co-Stimulatory Domains in CAR-T Cells for Optimal Functional Activity.

Cancers (Basel). 2022-1-8

[7]
A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells.

Mol Ther Oncolytics. 2021-11-11

[8]
CAR T-Cell Therapy: Is CD28-CAR Heterodimerization Its Achilles' Heel?

Front Immunol. 2021-11-17

[9]
A comprehensive comparison between camelid nanobodies and single chain variable fragments.

Biomark Res. 2021-12-4

[10]
Natural Flt3Lg-Based Chimeric Antigen Receptor (Flt3-CAR) T Cells Successfully Target Flt3 on AML Cell Lines.

Vaccines (Basel). 2021-10-25

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