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

Abstract

// Mizuho Sato-Dahlman 1 , Yoshiaki Miura 1 , Jing Li Huang 1 , Praveensingh Hajeri 1 , Kari Jacobsen 1 , Julia Davydova 1, 2 and Masato Yamamoto 1, 2, 3 1 Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA 2 Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA 3 Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA Correspondence to: Masato Yamamoto, email: yamam016@umn.edu 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.