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Published on: March 22, 2011
CD133-targeted oncolytic adenovirus demonstrates anti-tumor effect in colorectal cancer
Mizuho Sato-Dahlman1, Yoshiaki Miura1, Jing Li Huang1
1Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
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.
Insights
We developed a CD133-targeted Oncolytic Adenovirus (OAd) that selectively targets and destroys colorectal cancer stem cells. This OAd shows strong efficacy in preventing tumor formation and treating established tumors, offering a new approach for CRC treatment.
Area of Science:
- Oncolytic virotherapy
- Cancer stem cell targeting
- Colorectal cancer research
Background:
- Oncolytic Adenoviruses (OAds) are promising anti-cancer agents inducing cancer-specific cell death.
- Cancer stem cells (CSCs) drive colorectal cancer (CRC) recurrence, metastasis, and treatment resistance.
- Targeting CSCs is crucial for improving CRC treatment outcomes.
Purpose of the Study:
- To generate CD133-targeted OAd using an adenovirus library screening system.
- To evaluate the oncolytic activity of CD133-targeted OAd against colorectal cancer (CRC) in vitro and in vivo.
- To assess the potential of CD133-targeted OAd for preventing CRC recurrence and metastasis.
Main Methods:
- Generation of CD133-targeted OAd (AdML-TYML) via adenovirus library screening.
- In vitro assessment of AdML-TYML's infectivity and lysis of CD133+ CRC cells.
- In vivo studies in nude mice, including pre-tumor inoculation and intratumoral injection in established xenografts.
Main Results:
- AdML-TYML selectively infected and efficiently lysed CD133+ cultured CRC cells.
- Pre-treatment with AdML-TYML inhibited tumor establishment from CD133+ CRC cell lines in mice.
- Intratumoral injection of AdML-TYML demonstrated significant antitumor effects in established CD133+ CRC xenografts.
Conclusions:
- CD133-targeted OAd selectively targets and infects CD133+ colorectal cancer cells.
- AdML-TYML exhibits potent anti-tumorigenicity and therapeutic effects in established CRC tumors.
- This novel infectivity-selective OAd is a promising tool for preventing CRC metastasis and relapse.
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