Abstract 1903: Cancer stem cell vaccine significantly reduces local tumor relapse and prolongs survival in the adjuvant setting

Abstract

Abstract Although surgical resection has been a standard treatment for solid malignancies, therapeutic efficacy is limited by both local and distant recurrence. Effectively preventing local tumor recurrence remains a significant challenge. The existence of micro metastasis at the time of tumor resection represents an even greater therapeutic challenge, since 90% of tumor deaths are due to tumor metastasis. There is increasing evidence that many cancers are driven and maintained by a subpopulation of cells that display stem cell properties. Cancer stem cells (CSCs) can self-renew, mediate tumor growth and contribute to tumor recurrence and metastasis. Targeting CSCs may thus increase the therapeutic efficacy of current cancer treatment. We previously described a strategy to target CSCs using CSC-dendritic cell (DC) vaccination. However, the efficacy of CSC targeted therapeutics may be greatest when they are deployed in the adjuvant setting. In this study, two mouse models were utilized: SCC7 subcutaneous (s.c.) tumors, and a D5 melanoma model. Established s.c. SCC7 tumors were surgically removed from mice followed by treatment using ALDHhigh SCC7 CSC-DC vaccine, which significantly reduced local tumor relapse and prolonged animal survival. This effect was significantly augmented by simultaneous administration of anti-PD-L1 mAb. In the minimal disease setting of D5, ALDHhigh CSC-DC vaccination significantly inhibited tumor growth, reduced spontaneous lung metastases resulting in increased survival. CCR10 and its ligands were down-regulated on ALDHhigh D5 CSCs and in lung tissues respectively in animals subjected to ALDHhigh D5 CSC-DC vaccination. Down-regulation of CCR10 by siRNA significantly blocked tumor cell migration in vitro and metastasis in vivo. T cells harvested from ALDHhigh D5 CSC-DC vaccinated animals selectively killed the ALDHhigh D5 CSCs. There was also evidence of humoral immunological targeting of CSCs. As a result, CSC-DC vaccination significantly decreased the percentage of ALDHhigh cells in residual tumors. These data indicate that, when used in an adjuvant setting, ALDHhigh CSC-DC vaccines effectively inhibit local tumor recurrence, reduce spontaneous lung metastasis, and prolong animal survival; compared with traditional DC vaccines and that simultaneous PD-L1 blockade can significantly enhance this effect. Citation Format: Fei Liao, Yang yang Hu, Xin Chen, Alfed E Chang, Robert E Hollingsworth, Elaine Hurt, John Owen, Jeffrey S Moyer, Mark E.P Prince, Joel Whitfield, Yuxin Chu, Qibin Song, Max S Wicha, Qiao Li. Cancer stem cell vaccine significantly reduces local tumor relapse and prolongs survival in the adjuvant setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1903. doi:10.1158/1538-7445.AM2017-1903