SAMN21366618
External Id
Ben Gurion University of the Negev
INSDC center name
2022-09-01T01:45:00.633Z
INSDC first public
2022-09-01T01:45:00.633Z
INSDC last update
live
INSDC status
Human
NCBI submission model
Human.1.0
NCBI submission package
0
age
Prof Roi Gazit
biomaterial_provider
HEK293T
cell_line
Cancer immunotherapies are highly potent and are gaining wide clinical usage. However, severe side effects require focusing effector immune cell activities on the tumor microenvironment (TME). We recently developed a chimeric antigen receptor tumor-induced vector (CARTIV), a synthetic promoter activated by TME factors. To improve CARTIV functions including background, activation levels and synergism, we screened a library of promoters with variations in key positions. Here, we present a screening method involving turning ON/OFF stimulating TNFa and IFNg cytokines, followed by sequential cell sorting. Sequencing of enriched promoters identified seventeen candidates, which were cloned and whose activities were then validated, leading to identification of two CARTIVs with lower background and higher induction. We further combined a third hypoxia element with the two-factor CARTIV, demonstrating additional modular improvement. Our study presents a method of fine-tuning synthetic promoters for desired immunotherapy needs.
description
S1
isolate
Homo sapiens
http://purl.obolibrary.org/obo/NCBITaxon_9606
organism
human embryonic kidney
tissue
High Throughput Screen for the Improvement of Inducible Promoters for Tumor Microenvironment Cues
title