Oncotarget

Research Papers:

CD133-targeted oncolytic adenovirus demonstrates anti-tumor effect in colorectal cancer

Mizuho Sato-Dahlman, Yoshiaki Miura, Jing Li Huang, Praveensingh Hajeri, Kari Jacobsen, Julia Davydova and Masato Yamamoto _

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Oncotarget. 2017; 8:76044-76056. https://doi.org/10.18632/oncotarget.18340

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Abstract

Mizuho Sato-Dahlman1, Yoshiaki Miura1, Jing Li Huang1, Praveensingh Hajeri1, Kari Jacobsen1, Julia Davydova1,2 and Masato Yamamoto1,2,3

1Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA

2Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA

3Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA

Correspondence to:

Masato Yamamoto, email: [email protected]

Keywords: oncolytic adenovirus, targeting vector, colorectal cancer, CD133, cancer stem cells

Received: November 04, 2016     Accepted: April 19, 2017     Published: June 02, 2017

ABSTRACT

Oncolytic Adenoviruses (OAds) are one of the most promising anti-cancer agents that can induce cancer specific cell death. Recently, we generated infectivity-selective OAd, and the resultant OAd tumor-specific binding shows strong efficacy and mitigates toxicity. In this study, we applied this strategy based on adenovirus library screening system for generation of CD133-targeted OAd, and examined their oncolytic activity against colorectal cancer (CRC) in vitro and in vivo. CD133 (Prominin-1) is an important cell surface marker of cancer stem (like) cells (CSCs) in various cancers, including CRC. Elimination of CSCs has a high likelihood to improve CRC treatment because CSCs population in the tumor contributes to recurrence, metastases, chemotherapy resistance, and poor survival. The OAd with CD133-targeting motif (AdML-TYML) selectively infected CD133+ cultured cells and lysed them efficiently. Treatment with AdML-TYML prior to tumor inoculation inhibited the establishment of tumor of CD133+ CRC cell lines in nude mice. AdML-TYML also showed strong antitumor effect after intratumoral injections in already established CD133+ CRC subcutaneous xenografts. Our results indicate that CD133-targeted OAd selectively infected CD133+ CRC, and exhibited anti-tumorigenicity and therapeutic effect in established tumors. This novel infectivity selective virus could be a potent tool for the prevention of metastases and relapses in CRC.


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