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000305787 0247_ $$2doi$$a10.1038/s42003-021-01664-7
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000305787 037__ $$aDKFZ-2025-02404
000305787 041__ $$aEnglish
000305787 082__ $$a570
000305787 1001_ $$aGreenshpan, Yariv$$b0
000305787 245__ $$aSynthetic promoters to induce immune-effectors into the tumor microenvironment.
000305787 260__ $$aLondon$$bSpringer Nature$$c2021
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000305787 520__ $$aHarnessing 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.
000305787 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000305787 650_7 $$2NLM Chemicals$$aIFNG protein, human
000305787 650_7 $$2NLM Chemicals$$aNF-kappa B
000305787 650_7 $$2NLM Chemicals$$aReceptors, Chimeric Antigen
000305787 650_7 $$2NLM Chemicals$$aTNF protein, human
000305787 650_7 $$2NLM Chemicals$$aTumor Necrosis Factor-alpha
000305787 650_7 $$082115-62-6$$2NLM Chemicals$$aInterferon-gamma
000305787 650_2 $$2MeSH$$aAnimals
000305787 650_2 $$2MeSH$$aBreast Neoplasms: genetics
000305787 650_2 $$2MeSH$$aBreast Neoplasms: immunology
000305787 650_2 $$2MeSH$$aBreast Neoplasms: metabolism
000305787 650_2 $$2MeSH$$aBreast Neoplasms: therapy
000305787 650_2 $$2MeSH$$aCell Line, Tumor
000305787 650_2 $$2MeSH$$aFemale
000305787 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000305787 650_2 $$2MeSH$$aHEK293 Cells
000305787 650_2 $$2MeSH$$aHumans
000305787 650_2 $$2MeSH$$aImmunotherapy, Adoptive
000305787 650_2 $$2MeSH$$aInterferon-gamma: genetics
000305787 650_2 $$2MeSH$$aInterferon-gamma: pharmacology
000305787 650_2 $$2MeSH$$aKinetics
000305787 650_2 $$2MeSH$$aMice, Inbred NOD
000305787 650_2 $$2MeSH$$aNF-kappa B: genetics
000305787 650_2 $$2MeSH$$aPromoter Regions, Genetic
000305787 650_2 $$2MeSH$$aProof of Concept Study
000305787 650_2 $$2MeSH$$aReceptors, Chimeric Antigen: genetics
000305787 650_2 $$2MeSH$$aReceptors, Chimeric Antigen: metabolism
000305787 650_2 $$2MeSH$$aT-Lymphocytes: immunology
000305787 650_2 $$2MeSH$$aT-Lymphocytes: metabolism
000305787 650_2 $$2MeSH$$aT-Lymphocytes: transplantation
000305787 650_2 $$2MeSH$$aTumor Hypoxia
000305787 650_2 $$2MeSH$$aTumor Microenvironment
000305787 650_2 $$2MeSH$$aTumor Necrosis Factor-alpha: genetics
000305787 650_2 $$2MeSH$$aTumor Necrosis Factor-alpha: pharmacology
000305787 650_2 $$2MeSH$$aXenograft Model Antitumor Assays
000305787 650_2 $$2MeSH$$aMice
000305787 7001_ $$aSharabi, Omri$$b1
000305787 7001_ $$aOttolenghi, Aner$$b2
000305787 7001_ $$aCahana, Avishag$$b3
000305787 7001_ $$aKundu, Kiran$$b4
000305787 7001_ $$aM Yegodayev, Ksenia$$b5
000305787 7001_ $$aElkabets, Moshe$$b6
000305787 7001_ $$00000-0002-0548-2147$$aGazit, Roi$$b7
000305787 7001_ $$aPorgador, Angel$$b8
000305787 773__ $$0PERI:(DE-600)2919698-X$$a10.1038/s42003-021-01664-7$$gVol. 4, no. 1, p. 143$$n1$$p143$$tCommunications biology$$v4$$x2399-3642$$y2021
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