A recombinant adenovirus vector containing the synNotch receptor gene for the treatment of triple-negative breast cancer

A, Ruhan; Kunimura, Naoto; Tominaga, Shoko; Hirata, Erika; Nishioka, Shunya; Uesugi, Misato; Yamazaki, Rion; Ueki, Hideto; Kitagawa, Koichi; Fujisawa, Masato; Shirakawa, Toshiro

https://hdl.handle.net/20.500.14094/0100481920

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メタデータID	0100481920
アクセス権	open access
出版タイプ	Version of Record
タイトル	A recombinant adenovirus vector containing the synNotch receptor gene for the treatment of triple-negative breast cancer
著者	A, Ruhan ; Kunimura, Naoto ; Tominaga, Shoko ; Hirata, Erika ; Nishioka, Shunya ; Uesugi, Misato ; Yamazaki, Rion ; Ueki, Hideto ; Kitagawa, Koichi ; Fujisawa, Masato ; Shirakawa, Toshiro
著者名 A, Ruhan
著者名 Kunimura, Naoto
著者名 Tominaga, Shoko
著者名 Hirata, Erika
著者名 Nishioka, Shunya
著者名 Uesugi, Misato
著者名 Yamazaki, Rion
著者名 Ueki, Hideto
著者ID A2336 研究者ID 1000000822884 KUID https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=6dbda5319243ba9b520e17560c007669 著者名 Kitagawa, Koichi 北川, 孝一キタガワ, コウイチ所属機関名科学技術イノベーション研究科
著者ID A0878 研究者ID 1000030243314 KUID https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=57739d893d9102e6520e17560c007669 著者名 Fujisawa, Masato 藤澤, 正人フジサワ, マサト所属機関名医学研究科
著者ID A0776 研究者ID 1000070335446 KUID https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=e358a376badb297f520e17560c007669 著者名 Shirakawa, Toshiro 白川, 利朗シラカワ, トシロウ所属機関名科学技術イノベーション研究科
言語	English (英語)
収録物名	Frontiers in Oncology
巻(号)	13
ページ	1147668
出版者	Frontiers Media
刊行日	2023-03-29
公開日	2023-05-01
抄録	Triple-negative breast cancer (TNBC) is known as the most difficult molecular subtype of breast cancer to treat. Recent studies revealed that cancer stem cells (CSCs) play a critical role in TNBC recurrence and metastasis. In this study, we developed a recombinant replication-deficient adenoviral vector (Ad-CD44-N-HIF-3α4), 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)-3α4 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-3α4 is a dominant-negative regulator of HIF-1α and HIF-2α 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-3α4 is released from the Notch core domain. We performed an in vivo 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-HIF3α4. Our findings in this study warrant the further development of Ad-CD44-N-HIF3α4 for the treatment of patients with TNBC.
キーワード	adenovirus
	breast cancer
	gene therapy
	cancer stem cells
	HIF
カテゴリ	医学研究科
	科学技術イノベーション研究科
	学術雑誌論文
権利	© 2023 A, Kunimura, Tominaga, Hirata, Nishioka, Uesugi, Yamazaki, Ueki, Kitagawa, Fujisawa and Shirakawa.
権利	This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
関連情報	DOI https://doi.org/10.3389/fonc.2023.1147668

資源タイプ	journal article
eISSN	2234-943X　OPACで所蔵を検索　 CiNiiで学外所蔵を検索

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