文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

一种用于快速高效检测和富集嵌合抗原受体(CAR)T细胞的新型CD34衍生铰链区。

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

作者信息

Bister Arthur, Ibach Tabea, Haist Corinna, Smorra Denise, Roellecke Katharina, Wagenmann Martin, Scheckenbach Kathrin, Gattermann Norbert, Wiek Constanze, Hanenberg Helmut

机构信息

Department of Otorhinolaryngology, Head & Neck Surgery, Heinrich Heine University, 40225 Düsseldorf, Germany.

Department of Pediatrics III, University Children's Hospital, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany.

出版信息

Mol Ther Oncolytics. 2021 Nov 11;23:534-546. doi: 10.1016/j.omto.2021.11.003. eCollection 2021 Dec 17.


DOI:10.1016/j.omto.2021.11.003
PMID:34901395
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8640169/
Abstract

Immunotherapy including chimeric antigen receptor (CAR) T cell therapy has revolutionized modern cancer therapy and has achieved remarkable remission and survival rates for several malignancies with historically dismal outcomes. The hinge of the CAR connects the antigen binding to the transmembrane domain and can be exploited to confer features to CAR T cells including additional stimulation, targeted elimination or detection and enrichment of the genetically modified cells. For establishing a novel hinge derived from human CD34, we systematically tested CD34 fragments of different lengths, all containing the binding site of the QBend-10 monoclonal antibody, in a FMC63-based CD19 CAR lentiviral construct. A final construct of 99 amino acids called C6 proved to be the best candidate for flow cytometry-based detection of CAR T cells and >95% enrichment of genetically modified T cells on MACS columns. The C6 hinge was functionally indistinguishable from the commonly used CD8α hinge as well as in experiments in NSG mice. We also showed that the C6 hinge can be used for a variety of different CARs and mediates high killing efficacy without unspecific activation by target antigen-negative cells, thus making C6 ideally suited as a universal hinge for CARs for clinical applications.

摘要

免疫疗法,包括嵌合抗原受体(CAR)T细胞疗法,已经彻底改变了现代癌症治疗,并在几种以往预后不佳的恶性肿瘤中取得了显著的缓解率和生存率。CAR的铰链区将抗原结合与跨膜结构域相连,可用于赋予CAR T细胞一些特性,包括额外的刺激、靶向清除或对基因改造细胞的检测和富集。为了构建一种源自人CD34的新型铰链区,我们在基于FMC63的CD19 CAR慢病毒构建体中系统地测试了不同长度的CD34片段,所有片段都包含QBend-10单克隆抗体的结合位点。一种名为C6的99个氨基酸的最终构建体被证明是基于流式细胞术检测CAR T细胞以及在MACS柱上对基因改造T细胞进行>95%富集的最佳候选者。在NSG小鼠的实验中,C6铰链区在功能上与常用的CD8α铰链区没有区别。我们还表明,C6铰链区可用于多种不同的CAR,并介导高杀伤效力,而不会被靶抗原阴性细胞非特异性激活,因此C6非常适合作为临床应用中CAR的通用铰链区。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/fac3e68c39fa/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/4aea6e1e1a19/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/e4ad636daa7f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/6107962d81d3/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/f2ddadea3a07/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/9dc4364f62ff/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/2eafe46e5b1b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/069644457351/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/fac3e68c39fa/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/4aea6e1e1a19/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/e4ad636daa7f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/6107962d81d3/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/f2ddadea3a07/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/9dc4364f62ff/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/2eafe46e5b1b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/069644457351/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cc2/8640169/fac3e68c39fa/gr7.jpg

相似文献

[1]
A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells.

Mol Ther Oncolytics. 2021-11-11

[2]
Optimized NGFR-derived hinges for rapid and efficient enrichment and detection of CAR T cells and .

Mol Ther Oncolytics. 2022-6-6

[3]
Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains.

Mol Ther. 2017-7-27

[4]
A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines.

J Immunother Cancer. 2017-5-16

[5]
Genetic Engineering and Enrichment of Human NK Cells for CAR-Enhanced Immunotherapy of Hematological Malignancies.

Front Immunol. 2022

[6]
Hinge and Transmembrane Domains of Chimeric Antigen Receptor Regulate Receptor Expression and Signaling Threshold.

Cells. 2020-5-9

[7]
A Novel Siglec-4 Derived Spacer Improves the Functionality of CAR T Cells Against Membrane-Proximal Epitopes.

Front Immunol. 2020

[8]
Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells.

J Hematol Oncol. 2017-3-13

[9]
Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas.

J Immunother Cancer. 2023-11-24

[10]
A CD19/Fc fusion protein for detection of anti-CD19 chimeric antigen receptors.

J Transl Med. 2013-1-29

引用本文的文献

[1]
Expanding the CAR toolbox with high throughput screening strategies for CAR domain exploration: a comprehensive review.

J Immunother Cancer. 2025-4-9

[2]
Engineering resilient CAR T cells for immunosuppressive environment.

Mol Ther. 2025-6-4

[3]
The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.

Exp Hematol Oncol. 2024-12-4

[4]
Programmable synthetic receptors: the next-generation of cell and gene therapies.

Signal Transduct Target Ther. 2024-1-3

[5]
CAR-T cell potency: from structural elements to vector backbone components.

Biomark Res. 2022-9-19

[6]
Optimized NGFR-derived hinges for rapid and efficient enrichment and detection of CAR T cells and .

Mol Ther Oncolytics. 2022-6-6

[7]
Genetic Engineering and Enrichment of Human NK Cells for CAR-Enhanced Immunotherapy of Hematological Malignancies.

Front Immunol. 2022

本文引用的文献

[1]
Epigenetic Priming of Bladder Cancer Cells With Decitabine Increases Cytotoxicity of Human EGFR and CD44v6 CAR Engineered T-Cells.

Front Immunol. 2021

[2]
CD44v6-targeted CAR T-cells specifically eliminate CD44 isoform 6 expressing head/neck squamous cell carcinoma cells.

Oral Oncol. 2021-5

[3]
Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany.

Gene Ther. 2021-9

[4]
Recent advances and discoveries in the mechanisms and functions of CAR T cells.

Nat Rev Cancer. 2021-3

[5]
Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.

Lancet. 2020-9-1

[6]
Accurate In-Vivo Quantification of CD19 CAR-T Cells after Treatment with Axicabtagene Ciloleucel (Axi-Cel) and Tisagenlecleucel (Tisa-Cel) Using Digital PCR.

Cancers (Basel). 2020-7-20

[7]
The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice.

Front Immunol. 2020

[8]
Hinge and Transmembrane Domains of Chimeric Antigen Receptor Regulate Receptor Expression and Signaling Threshold.

Cells. 2020-5-9

[9]
Excellent proliferation and persistence of allogeneic donor-derived 41-BB based CAR-T cells despite immunosuppression with cyclosporine A.

Haematologica. 2020-6

[10]
Anti-CAR-engineered T cells for epitope-based elimination of autologous CAR T cells.

Cancer Immunol Immunother. 2019-8-14

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索