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In this study, we developed a recombinant replication-deficient adenoviral vector (Ad-CD44-N-HIF-3\u03b14), which contains a gene encoding a synthetic Notch (synNotch) receptor composed of the extracellular domain of CD44 (CD44-ECD) and the hypoxia-inducible factor (HIF)-3\u03b14 connected by the Notch core regulatory region. CD44 is a transmembrane glycoprotein and known as a CSC marker in breast cancer and other malignancies. HIF-3\u03b14 is a dominant-negative regulator of HIF-1\u03b1 and HIF-2\u03b1 and inhibits hypoxia-inducing effect. Both CD44 and HIF signals contribute cancer stemness and maintaining CSCs in breast cancer. The CD44-ECD in the synNotch receptor acts as the CD44 decoy receptor, and after a ligand such as a hyaluronic acid binds to the CD44-ECD, HIF-3\u03b14 is released from the Notch core domain. We performed an <jats:italic>in vivo<\/jats:italic> study using a mouse xenograft model of MDA-MB-231, a highly invasive TNBC cell, and confirmed the significant antitumor activity of the intratumoral injections of Ad-CD44-N-HIF3\u03b14. Our findings in this study warrant the further development of Ad-CD44-N-HIF3\u03b14 for the treatment of patients with TNBC.<\/jats:p>","DOI":"10.3389\/fonc.2023.1147668","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T17:59:40Z","timestamp":1680112780000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A recombinant adenovirus vector containing the synNotch receptor gene for the treatment of triple-negative breast 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