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最小启动子元件对肿瘤微环境中介导 CAR 表达的合成启动子活性的贡献

英文原题:The Contribution of the Minimal Promoter Element to the Activity of Synthetic Promoters Mediating CAR Expression in the Tumor Microenvironment.

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The Contribution of the Minimal Promoter Element to the Activity of Synthetic Promoters Mediating CAR Expression in the Tumor Microenvironment.

PubMed 2022/07/04(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

近年来,利用免疫效应细胞造福癌症患者的做法日益普遍。然而,嵌合抗原受体及装甲型CAR等治疗策略不断增加,要求持续调整转基因表达水平。我们此前已利用嵌合抗原受体肿瘤诱导载体(CARTIV)平台,实现转基因表达的时空控制,并可定制诱导剂。本文介绍该启动子平台进一步的定制化进展。我们测试了三个强度不同的最小启动子,由此产生不同水平的CAR表达并影响原代T细胞功能。这一策略为CARTIV基因调控增加了新的层次,可轻松整合到现有CAR-T 系统中。

展开英文摘要原文

Harnessing immune effector cells to benefit cancer patients is becoming more and more prevalent in recent years.

However, the increasing number of different therapeutic approaches, such as chimeric antigen receptors and armored chimeric antigen receptors, requires constant adjustments of the transgene expression levels.

We have previously demonstrated it is possible to achieve spatial and temporal control of transgene expression as well as tailoring the inducing agents using the Chimeric Antigen Receptor Tumor Induced Vector (CARTIV) platform.

Here we describe the next level of customization in our promoter platform.

We have tested the functionality of three different minimal promoters, representing three different promoters' strengths, leading to varying levels of CAR expression and primary T cell function. This strategy shows yet another level of CARTIV gene regulation that can be easily integrated into existing CAR T systems.

论文信息

作者
Greenshpan Y、Sharabi O、Yegodayev KM、Novoplansky O、Elkabets M、Gazit R、Porgador A
单位
The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.Israel
期刊
International journal of molecular sciences2022 Jul 4
原文标识
PubMed 35806439 · DOI 10.3390/ijms23137431

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