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

一种用于癌症免疫治疗的通用嵌合抗原受体(CAR)-片段抗体结合物(FAB)拆分系统。

A universal chimeric antigen receptor (CAR)-fragment antibody binder (FAB) split system for cancer immunotherapy.

作者信息

Arina Ainhoa, Arauz Edwin, Masoumi Elham, Warzecha Karolina W, Sääf Annika, Widło Łukasz, Slezak Tomasz, Zieminska Aleksandra, Dudek Karolina, Schaefer Zachary P, Lecka Maria, Usatyuk Svitlana, Weichselbaum Ralph R, Kossiakoff Anthony A

机构信息

Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, USA.

Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.

出版信息

Sci Adv. 2025 Jul 4;11(27):eadv4937. doi: 10.1126/sciadv.adv4937.


DOI:10.1126/sciadv.adv4937
PMID:40614208
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12227065/
Abstract

Chimeric antigen receptor (CAR) T cell therapy has shown extraordinary results in treating hematological cancer but faces challenges like antigen loss, toxicity, and complex manufacturing. Universal and modular CAR constructs offer improved flexibility, safety, and cost-effectiveness over conventional CAR constructs. We present a CAR-fragment antibody binder (Fab) platform on the basis of an engineered protein G variant (GA1) and Fab scaffolds. Expression of GA1CAR on human CD8 T cells leads to antigen recognition and T cell effector function that can be modulated according to the affinity of the CAR for the Fab and of the Fab for the target. GA1CAR T cells can recognize multiple Fab-antigen pairs on breast and ovarian cancer cell lines. Adoptively transferred GA1CAR T cells control tumors in breast cancer xenograft models, and their targeting can be quickly redirected using different Fabs. This versatile "plug-and-play" CAR T platform has potential for application in personalized therapy, preventing antigen loss variant escape, decreasing toxicity, and increasing access.

摘要

嵌合抗原受体(CAR)T细胞疗法在治疗血液系统癌症方面已显示出非凡的效果,但面临着抗原丢失、毒性和复杂制造等挑战。通用型和模块化CAR构建体比传统CAR构建体具有更高的灵活性、安全性和成本效益。我们基于工程化蛋白G变体(GA1)和Fab支架提出了一种CAR片段抗体结合物(Fab)平台。GA1CAR在人CD8 T细胞上的表达导致抗原识别和T细胞效应功能,可根据CAR对Fab以及Fab对靶标的亲和力进行调节。GA1CAR T细胞能够识别乳腺癌和卵巢癌细胞系上的多个Fab-抗原对。过继转移的GA1CAR T细胞可控制乳腺癌异种移植模型中的肿瘤,并且使用不同的Fab可快速重新定向其靶向。这种多功能的“即插即用”CAR T平台在个性化治疗、防止抗原丢失变体逃逸、降低毒性以及增加可及性方面具有应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/f602bd60ee06/sciadv.adv4937-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/179ce765a749/sciadv.adv4937-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/dcc69692ba34/sciadv.adv4937-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/db55919efcb1/sciadv.adv4937-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/87931e16a186/sciadv.adv4937-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/fcd19ff3f8a2/sciadv.adv4937-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/f602bd60ee06/sciadv.adv4937-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/179ce765a749/sciadv.adv4937-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/dcc69692ba34/sciadv.adv4937-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/db55919efcb1/sciadv.adv4937-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/87931e16a186/sciadv.adv4937-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/fcd19ff3f8a2/sciadv.adv4937-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b2/12227065/f602bd60ee06/sciadv.adv4937-f6.jpg

相似文献

[1]
A universal chimeric antigen receptor (CAR)-fragment antibody binder (FAB) split system for cancer immunotherapy.

Sci Adv. 2025-7-4

[2]
Utilization of universal-targeting mSA2 CAR-T cells for the treatment of glioblastoma.

Oncoimmunology. 2025-12

[3]
A Switch Protein Adapter for Anti-LILRB4 CAR-T Cells.

Eur J Immunol. 2025-2

[4]
Bystander CARCD8 T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody.

J Immunother Cancer. 2025-6-24

[5]
Transduction of γδ T cells with Baboon envelope pseudotyped lentiviral vector encoding chimeric antigen receptors for translational and clinical applications.

Front Immunol. 2025-6-6

[6]
Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner.

Mol Ther. 2025-1-3

[7]
ADI-270: an armored allogeneic gamma delta T cell therapy designed to target CD70-expressing solid and hematologic malignancies.

J Immunother Cancer. 2025-7-1

[8]
GITRL enhances cytotoxicity and persistence of CAR-T cells in cancer therapy.

Mol Ther. 2025-6-4

[9]
Membrane-bound IL-7 immobilized by the CD8 transmembrane region improves efficacy of CD19 CAR-T cell therapy.

Mol Cancer. 2024-10-23

[10]
Recent advances on anti-HIV chimeric antigen receptor-T-cell treatment to provide sustained HIV remission.

Curr Opin HIV AIDS. 2024-7-1

本文引用的文献

[1]
Engineered protein G variants for multifunctional antibody-based assemblies.

Protein Sci. 2025-2

[2]
CAR immune cells: design principles, resistance and the next generation.

Nature. 2023-2

[3]
Four challenges to CAR T cells breaking the glass ceiling.

Eur J Immunol. 2023-11

[4]
Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours.

Nat Rev Clin Oncol. 2023-1

[5]
Gene-edited healthy donor CAR T cells show superior anti-tumour activity compared to CAR T cells derived from patients with lymphoma in an in vivo model of high-grade lymphoma.

Leukemia. 2021-12

[6]
Navigating CAR-T cells through the solid-tumour microenvironment.

Nat Rev Drug Discov. 2021-7

[7]
CAR-T cell therapy: current limitations and potential strategies.

Blood Cancer J. 2021-4-6

[8]
CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?

Mol Ther. 2020-11-4

[9]
A Distinct Transcriptional Program in Human CAR T Cells Bearing the 4-1BB Signaling Domain Revealed by scRNA-Seq.

Mol Ther. 2020-12-2

[10]
Hinge and Transmembrane Domains of Chimeric Antigen Receptor Regulate Receptor Expression and Signaling Threshold.

Cells. 2020-5-9

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