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CAR T 细胞疗法的世代、批准和临床试验的最新进展。

Current updates on generations, approvals, and clinical trials of CAR T-cell therapy.

机构信息

Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

Department of Biochemistry, College of Medicine and Health Science Arbaminch University, Arbaminch, Ethiopia.

出版信息

Hum Vaccin Immunother. 2022 Nov 30;18(6):2114254. doi: 10.1080/21645515.2022.2114254. Epub 2022 Sep 12.


DOI:10.1080/21645515.2022.2114254
PMID:36094837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9746433/
Abstract

Chimeric antigen receptor (CAR) T-cell therapy is a novel, customized immunotherapy that is considered a 'living' and self-replicating drug to treat cancer, sometimes resulting in a complete cure. CAR T-cells are manufactured through genetic engineering of T-cells by equipping them with CARs to detect and target antigen-expressing cancer cells. CAR is designed to have an ectodomain extracellularly, a transmembrane domain spanning the cell membrane, and an endodomain intracellularly. Since its first discovery, the CAR structure has evolved greatly, from the first generation to the fifth generation, to offer new therapeutic alternatives for cancer patients. This treatment has achieved long-term and curative therapeutic efficacy in multiple blood malignancies that nowadays profoundly change the treatment landscape of lymphoma, leukemia, and multiple myeloma. But CART-cell therapy is associated with several hurdles, such as limited therapeutic efficacy, little effect on solid tumors, adverse effects, expensive cost, and feasibility issues, hindering its broader implications.

摘要

嵌合抗原受体 (CAR) T 细胞疗法是一种新型的、定制化的免疫疗法,被认为是一种“活的”、自我复制的药物,可以治疗癌症,有时甚至可以实现完全治愈。CAR T 细胞是通过对 T 细胞进行基因工程改造而制成的,方法是为它们配备 CAR,以检测和靶向表达抗原的癌细胞。CAR 的设计具有细胞外的外显子结构域、跨膜结构域和细胞内的内显子结构域。自首次发现以来,CAR 结构已经发生了很大的演变,从第一代发展到第五代,为癌症患者提供了新的治疗选择。这种治疗方法在多种血液恶性肿瘤中取得了长期的、治愈性的疗效,如今深刻地改变了淋巴瘤、白血病和多发性骨髓瘤的治疗格局。但是,CAR-T 细胞疗法存在一些障碍,例如治疗效果有限、对实体瘤效果不大、不良反应、昂贵的成本和可行性问题,这些都限制了其更广泛的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/f7e67abaaac2/KHVI_A_2114254_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/77ed75048105/KHVI_A_2114254_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/a0ca6f41333f/KHVI_A_2114254_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/d3a9caebcc94/KHVI_A_2114254_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/f7e67abaaac2/KHVI_A_2114254_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/77ed75048105/KHVI_A_2114254_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/a0ca6f41333f/KHVI_A_2114254_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/d3a9caebcc94/KHVI_A_2114254_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1b/9746433/f7e67abaaac2/KHVI_A_2114254_F0004_OC.jpg

相似文献

[1]
Current updates on generations, approvals, and clinical trials of CAR T-cell therapy.

Hum Vaccin Immunother. 2022-11-30

[2]
Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist.

Oncologist. 2016-5

[3]
Perspectives on Chimeric Antigen Receptor T-Cell Immunotherapy for Solid Tumors.

Front Immunol. 2018-5-22

[4]
Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter Generations of Chimeric Antigen Receptor T Cells.

Front Immunol. 2018-7-31

[5]
Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives.

Curr Res Transl Med. 2017-9

[6]
Driving CARs on the Highway to Solid Cancer: Some Considerations on the Adoptive Therapy with CAR T Cells.

Hum Gene Ther. 2017-8-15

[7]
Engineering CAR-T Cells for Next-Generation Cancer Therapy.

Cancer Cell. 2020-10-12

[8]
CAR T-Cell Therapy in Hematological Malignancies.

Int J Mol Sci. 2021-8-20

[9]
Treatment of solid tumors with chimeric antigen receptor-engineered T cells: current status and future prospects.

Sci China Life Sci. 2016-3-11

[10]
Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells.

Cytotherapy. 2016-11

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

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

[3]
Tracing the development of CAR-T cell design: from concept to next-generation platforms.

Front Immunol. 2025-7-17

[4]
Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.

Curr Issues Mol Biol. 2025-4-10

[5]
Advancing CAR-based cell therapies for solid tumours: challenges, therapeutic strategies, and perspectives.

Mol Cancer. 2025-7-7

[6]
CAR-T cell therapy for cancer: current challenges and future directions.

Signal Transduct Target Ther. 2025-7-4

[7]
Enhancing mesothelin CAR T cell therapy for pancreatic cancer with an oncolytic herpes virus boosting CAR target antigen expression.

Cancer Immunol Immunother. 2025-5-14

[8]
Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma.

Biomark Res. 2025-5-1

[9]
SynNotch CAR-T cell, when synthetic biology and immunology meet again.

Front Immunol. 2025-4-16

[10]
Identification of M2 macrophage-related genes associated with diffuse large B-cell lymphoma via bioinformatics and machine learning approaches.

Biol Direct. 2025-4-29

本文引用的文献

[1]
Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer.

Biomedicines. 2022-6-24

[2]
Overview of approved CAR-T therapies, ongoing clinical trials, and its impact on clinical practice.

EJHaem. 2021-11-24

[3]
Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia.

Blood Cancer J. 2022-6-24

[4]
Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas.

Ann Oncol. 2022-9

[5]
De novo-designed transmembrane domains tune engineered receptor functions.

Elife. 2022-5-4

[6]
A novel adoptive synthetic TCR and antigen receptor (STAR) T-Cell therapy for B-Cell acute lymphoblastic leukemia.

Am J Hematol. 2022-8

[7]
Enhanced safety and efficacy of protease-regulated CAR-T cell receptors.

Cell. 2022-5-12

[8]
Anakinra utilization in refractory pediatric CAR T-cell associated toxicities.

Blood Adv. 2022-6-14

[9]
Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial.

Nat Med. 2022-4

[10]
HLA-independent T cell receptors for targeting tumors with low antigen density.

Nat Med. 2022-2

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