Characterization of sarcoma stem cells and development of the stem cell-targeting agents utilizing viral engineering

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The purpose of this study is to concentrate the stem (tumor-initiating) cell fraction of sarcoma, and then to develop stem cell-targeted agent, utilizing cell-targeting technologies with oncolytic virus. Several lines of highly tumorigenic osateosarcoma were isolated. Tumor-initiating cells from gastrointestinal stromal tumor, sarcoma-like tumor, were concentrated into the cellular fraction characterized with the cell surface marker CD133(Low/-) in vitro. Those cells were shown to be silenced in the hypoxic region of tumor, and resistant to Imatinib treatment. Tumor-initiating cells from sarcomatous mesothelioma were concentrated into the cellular fraction with CD133 (Low/-) and CD44(+). We showed that our HSV-1 oncolytic virus d12ODDΔRR targeting hypoxic microenvironment of tumor successfully destroyed tumor-initiating cells from stromal tumor and mesothelioma.