用于 CAR-T 细胞特异性疗效和安全性测试的乳腺癌芯片

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2024-05-15 DOI:10.1016/j.stem.2024.04.018
Tengku Ibrahim Maulana, Claudia Teufel, Madalena Cipriano, Julia Roosz, Lisa Lazarevski, Francijna E. van den Hil, Lukas Scheller, Valeria Orlova, André Koch, Michael Hudecek, Miriam Alb, Peter Loskill
{"title":"用于 CAR-T 细胞特异性疗效和安全性测试的乳腺癌芯片","authors":"Tengku Ibrahim Maulana, Claudia Teufel, Madalena Cipriano, Julia Roosz, Lisa Lazarevski, Francijna E. van den Hil, Lukas Scheller, Valeria Orlova, André Koch, Michael Hudecek, Miriam Alb, Peter Loskill","doi":"10.1016/j.stem.2024.04.018","DOIUrl":null,"url":null,"abstract":"<p>Physiologically relevant human models that recapitulate the challenges of solid tumors and the tumor microenvironment (TME) are highly desired in the chimeric antigen receptor (CAR)-T cell field. We developed a breast cancer-on-chip model with an integrated endothelial barrier that enables the transmigration of perfused immune cells, their infiltration into the tumor, and concomitant monitoring of cytokine release during perfused culture over a period of up to 8 days. Here, we exemplified its use for investigating CAR-T cell efficacy and the ability to control the immune reaction with a pharmacological on/off switch. Additionally, we integrated primary breast cancer organoids to study patient-specific CAR-T cell efficacy. The modular architecture of our tumor-on-chip paves the way for studying the role of other cell types in the TME and thus provides the potential for broad application in bench-to-bedside translation as well as acceleration of the preclinical development of CAR-T cell products.</p>","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"47 1","pages":""},"PeriodicalIF":19.8000,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells\",\"authors\":\"Tengku Ibrahim Maulana, Claudia Teufel, Madalena Cipriano, Julia Roosz, Lisa Lazarevski, Francijna E. van den Hil, Lukas Scheller, Valeria Orlova, André Koch, Michael Hudecek, Miriam Alb, Peter Loskill\",\"doi\":\"10.1016/j.stem.2024.04.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Physiologically relevant human models that recapitulate the challenges of solid tumors and the tumor microenvironment (TME) are highly desired in the chimeric antigen receptor (CAR)-T cell field. We developed a breast cancer-on-chip model with an integrated endothelial barrier that enables the transmigration of perfused immune cells, their infiltration into the tumor, and concomitant monitoring of cytokine release during perfused culture over a period of up to 8 days. Here, we exemplified its use for investigating CAR-T cell efficacy and the ability to control the immune reaction with a pharmacological on/off switch. Additionally, we integrated primary breast cancer organoids to study patient-specific CAR-T cell efficacy. The modular architecture of our tumor-on-chip paves the way for studying the role of other cell types in the TME and thus provides the potential for broad application in bench-to-bedside translation as well as acceleration of the preclinical development of CAR-T cell products.</p>\",\"PeriodicalId\":9665,\"journal\":{\"name\":\"Cell stem cell\",\"volume\":\"47 1\",\"pages\":\"\"},\"PeriodicalIF\":19.8000,\"publicationDate\":\"2024-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell stem cell\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stem.2024.04.018\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell stem cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stem.2024.04.018","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

摘要

嵌合抗原受体(CAR)-T 细胞领域非常需要能再现实体瘤和肿瘤微环境(TME)挑战的生理相关人体模型。我们开发了一种集成了内皮屏障的乳腺癌芯片模型,它能使灌注的免疫细胞迁移、浸润到肿瘤中,并在长达 8 天的灌注培养过程中同时监测细胞因子的释放。在这里,我们举例说明了它在研究 CAR-T 细胞疗效方面的用途,以及通过药理开关控制免疫反应的能力。此外,我们还整合了原发性乳腺癌器官组织来研究患者特异性 CAR-T 细胞的疗效。我们的肿瘤芯片的模块化结构为研究TME中其他细胞类型的作用铺平了道路,从而为从台架到床边的转化提供了广泛的应用潜力,并加速了CAR-T细胞产品的临床前开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells

Physiologically relevant human models that recapitulate the challenges of solid tumors and the tumor microenvironment (TME) are highly desired in the chimeric antigen receptor (CAR)-T cell field. We developed a breast cancer-on-chip model with an integrated endothelial barrier that enables the transmigration of perfused immune cells, their infiltration into the tumor, and concomitant monitoring of cytokine release during perfused culture over a period of up to 8 days. Here, we exemplified its use for investigating CAR-T cell efficacy and the ability to control the immune reaction with a pharmacological on/off switch. Additionally, we integrated primary breast cancer organoids to study patient-specific CAR-T cell efficacy. The modular architecture of our tumor-on-chip paves the way for studying the role of other cell types in the TME and thus provides the potential for broad application in bench-to-bedside translation as well as acceleration of the preclinical development of CAR-T cell products.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
期刊最新文献
Generation of iPSC-derived human venous endothelial cells for the modeling of vascular malformations and drug discovery Post-transplant G-CSF impedes engraftment of gene-edited human hematopoietic stem cells by exacerbating p53-mediated DNA damage response Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity All roads lead to cholesterol: Modulating lipid biosynthesis in multiple sclerosis patient-derived models
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1