Synthetic promoters to induce immune-effectors into the tumor microenvironment

Yariv Greenshpan, Omri Sharabi, Aner Ottolenghi, Avishag Cahana, Kiran Kundu, Ksenia M. Yegodayev, Moshe Elkabets, Roi Gazit, Angel Porgador

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Harnessing the immune-system to eradicate cancer is becoming a reality in recent years. Engineered immune cells, such as chimeric antigen receptor (CAR) T cells, are facing the danger of an overt life-threatening immune response due to the ON-target OFF-tumor cytotoxicity and Cytokine Release Syndrome. We therefore developed synthetic promoters for regulation of gene expression under the control of inflammation and Hypoxia-induced signals that are associated with the tumor microenvironment (TME). We termed this methodology as chimeric-antigen-receptor-tumor-induced-vector (CARTIV). For proof of concept, we studied synthetic promoters based on promoter-responsive elements (PREs) of IFNγ, TNFα and hypoxia; triple PRE-based CARTIV promoter manifested a synergistic activity in cell-lines and potent activation in human primary T-cells. CARTIV platform can improve safety of CAR T-cells or other engineered immune-cells, providing TME-focused activity and opening a therapeutic window for many tumor-associated antigens that are also expressed by non-tumor healthy tissues.

Original languageEnglish
Article number143
JournalCommunications Biology
Issue number1
StatePublished - 1 Dec 2021

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Agricultural and Biological Sciences (all)


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