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

Autor: Greenshpan Y; The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.; National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel., Sharabi O; The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.; National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel., Yegodayev KM; The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel., Novoplansky O; The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel., Elkabets M; The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel., Gazit R; The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.; National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel., Porgador A; The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.; National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Jul 04; Vol. 23 (13). Date of Electronic Publication: 2022 Jul 04.
DOI: 10.3390/ijms23137431
Abstrakt: 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.
Databáze: MEDLINE
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