Abstract

Abstract The inability to target cancer stem cells (CSC) may be a significant factor contributing to treatment failure. Novel therapeutic strategies are needed to immunologically target CSCs. We have developed a strategy to target the CSC populations in melanoma and squamous cell carcinoma using CSC lysate-pulsed dendritic cells (DC). Using mouse models we demonstrate that DC pulsed with CSCs enriched by virtue of their expression of the CSC marker ALDH (CSC-DC) significantly inhibited local tumor growth, reduced development of pulmonary metastases and prolonged survival in the minimal tumor models. The effect was associated with down regulation of CCR7 and CCR10 in tumor cells and decreased CCL27 and CCL28 expression in lung tissue. CSC-DC vaccine significantly reduced ALDHhigh CSCs. Direct targeting of CSCs was demonstrated by specific binding of IgG produced by ALDHhigh CSC-DC vaccine-primed B cells to ALDHhigh CSCs, resulting in lysis of these target cells in the presence of complement. When administered in the adjuvant setting after surgical excision of the bulk tumor mass, administration of CSC-DC vaccine reduced development of local tumor growth as well as systemic disease and prolonged survival demonstrating the efficacy of this approach. These data suggest that the CSC-DC vaccine approach may be useful in the adjuvant setting where local and systemic relapse are high after surgery. Note: This abstract was not presented at the meeting. Citation Format: Yangyang Hu, Lin Lu, Alfred E. Chang, Martin Egenti, John Owen, Jeffrey S. Moyer, Mark E.P. Prince, Jianchuan Xia, Shiang Huang, Max S. Wicha, Qiao Li. Therapeutic efficacy of cancer stem cell vaccine in an adjuvant setting. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1530. doi:10.1158/1538-7445.AM2015-1530

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