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

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 8_Supplement; p. 4185
• Main Authors: Liu, Zhigang, Zhao, Xiumei, Adesina, Adenkunle M., Baxter, Patricia, Zhao, Yijue, Rao, Pulavalti, Su, Jack M., Perlaky, Lazlo, Dauser, Robert, Chintagumpala, Murali, Lau, Ching C., Blaney, Susan M., Li, Xiao-Nan
• Format: Journal Article
• Language: English
• Published: 15.04.2010
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-4185

Abstract 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.