Abstract 4185: Isolation of cancer stem-like cells from a novel orthotopic xenograt model of supratentorial primitive neuroectodermal tumor that is susceptible to oncolytic Seneca Valley Virus
| Autor: | Robert C. Dauser, Susan M. Blaney, Zhigang Liu, Ching C. Lau, Jack Su, Xiao-Nan Li, Patricia Baxter, Lazlo Perlaky, Yi-Jue Zhao, Xiumei Zhao, Adenkunle M. Adesina, Murali Chintagumpala, Pulavalti Rao |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:4185-4185 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am10-4185 |
| Popis: | Purpose: Supratentorial primitive neuroectodermal tumor (PNET) accounts for 2-3% of all pediatric brain tumors. Despite multimodality therapies, the clinical outcome remains poor, and the 5-year progression free survival rate is less than 40%. Clinically relevant animal models are needed for understanding tumor biology and developing more effective therapies. Here we report our recent development of a clinically relevant animal model, isolation and characterization of cancer stem-like cells in the xenograft tumors, and preclinical investigation of the antitumor efficacy of a novel picorna oncolytic virus Seneca Valley Virus-001 (SVV-001) both in vitro and vivo, especially in cancer stem-like cells. Experimental Design: Orthotopic xenograft mouse model was developed by direct injection of 105 tumor cells from a freshly resected brain PNET tumor specimen into the right cerebrum of Rag2/severe combined immunodeficient mice. CD133+ cells were quantitatively analyzed and isolated with FACS using human-specific antibodies against CD133. Antitumor activity of SVV-001was evaluated in vitro in cultured xenograft tumor cells and in vivo in mice bearing pre-formed xenograft tumors. Results: A novel transplantable PNET xenograft model IC-2664PNT was established. The xenograft tumors not only replicate the biologic phenotypes but also preserve cancer stem-like cell pools. The IC-2664PNET neurospheres, which expressed high levels of CD133 and nestin, were efficiently infected and killed by SVV-001 (0.5-25 virus particle/ cell). A single tail vein injection of SVV-001 (5×1012 virus particle/kg) prolonged survival time of PNET xenograft model. Conclusions: We have established the first clinically relevant animal model for childhood supratentorial PNET. It replicated the major histopathological features of the original patient tumor, and preserved a CD133+ stem cells pool during serial subtransplantations. SVV-001 has potent antitumor efficacy in PNET, especially selectively kill cancer stem-like cells, and prolong survival in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4185. |
| Databáze: | OpenAIRE |
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