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

Yariv Greenshpan; Omri Sharabi; Ksenia M Yegodayev; Ofra Novoplansky; Moshe Elkabets; Roi Gazit; Angel Porgador

doi:10.3390/ijms23137431

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

Int J Mol Sci. 2022 Jul 4;23(13):7431. doi: 10.3390/ijms23137431.

Authors

Yariv Greenshpan^{1

2}, Omri Sharabi^{1

2}, Ksenia M Yegodayev¹, Ofra Novoplansky¹, Moshe Elkabets¹, Roi Gazit^{1

2}, Angel Porgador^{1

2}

Affiliations

¹ The Shraga Segal Department of Microbiology, Faculty of Health Sciences, Immunology and Genetics, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
² National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.

Abstract

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.

Keywords: CARTIV; chimeric antigen receptor; minimal promoter; synthetic promoter.

MeSH terms

Humans
Immunotherapy, Adoptive
Neoplasms* / metabolism
Promoter Regions, Genetic
Receptors, Antigen, T-Cell / metabolism
Receptors, Chimeric Antigen*
T-Lymphocytes
Tumor Microenvironment / genetics

Substances

Receptors, Antigen, T-Cell
Receptors, Chimeric Antigen

Grants and funding

This research was funded by: Israel Science Foundation grant: 2484/19 (A.P.) and 883/21 (R.G.); ISF-NRF: 3127/19 (A.P.); DKFZ-MOST grant: CA194 (A.P.); United States-Israel Binational Science Foundation: 2019377 (A.P.); Ministry of Health: 3-15080 (R.G. and A.P.).