Abstract 749: Cancer stem cell vaccination confers significant anti-tumor immunity by selectively targeting cancer stem cells

Abstract

Abstract To date, the majority of cancer stem cell (CSC) studies have been confined to human tumors inoculated into severely immunosuppressed hosts (e.g. SCID mice), where adaptive immune responses are absent, and such hosts are therefore not suitable for immunologic evaluation. The lack of immunocompetent syngeneic animal tumor models where stem cells can be isolated has been the primary obstacle to evaluating the immunogenicity of CSCs. In this study, we identified CSC-enriched populations in two histologically distinct murine tumors (melanoma B16-D5 and squamous cell cancer SCC7). We found that a very small percentage (0.5-5%) of ALDEFLUOR/ALDH1+ cells exist in these tumors; as few as 500 sorted ALDEFLUOR+ cells could form tumors in syngeneic hosts. The stem cell nature of the ALDELFUOR+ cells was confirmed by their ability to form spheres in culture and to self-renew in vivo. We evaluated the protective anti-tumor responses induced by D5 cancer stem cell-based vaccination with dendritic cell in the syngeneic immunocompetent host (B6 mice) in a pulmonary metastatic setting. We found that enriched D5 CSCs are immunogenic and are significantly more effective as an antigen source compared with unselected D5 tumor cells in inducing protective anti-tumor immunity. CSC-induced protective antitumor immunity was confirmed in a second tumor model (SCC7) syngeneic to a genetically different immunocompetent host (C3H) in a subcutaneous tumor setting. Immune sera collected from D5 or SCC7 CSC-vaccinated hosts contain high levels of IgG and IgG2b which bound specifically to D5 CSCs or SCC7 CSCs, respectively. This binding resulted in the CSC lysis in the presence of complement. In addition, CTLs generated from PBMCs harvested from D5 or SCC7 CSC-vaccinated hosts selectively killed D5 or SCC7 CSCs efficiently. We provide the first direct experimental evidence that selective targeting of cancer stem cells by CSC-primed antibodies and T cells may represent the mechanisms involved in CSC vaccine-conferred anti-tumor immunity. The findings from these studies may help develop novel cancer stem cell-targeted immunological approaches for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 749. doi:10.1158/1538-7445.AM2011-749