Qiao Li
University Of Michigan Comprehensive Cancer Center, USA
Title: Generation And Application Of Cancer Stem Cell Vaccine In The Adjuvant Setting
Biography
Biography: Qiao Li
Abstract
Effective prevention of local and distant 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 cancer stem cells (CSCs) which contribute to tumor recurrence and metastasis. Targeting CSCs may thus increase the therapeutic efficacy of current cancer treatment. We 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: Established s.c. SCC7 tumors were surgically removed from mice followed by treatment using ALDH (high) 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 melanoma, ALDH (high) CSC-DC vaccination significantly inhibited tumor growth, reduced spontaneous lung metastases resulting in increased survival. CCR10 and its ligands were down-regulated on ALDH (high) D5 CSCs and in lung tissues, respectively in animals subjected to ALDH (high) 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 ALDH (high) D5 CSC-DC vaccinated animals selectively killed the ALDH (high) D5 CSCs. As a result, CSC-DC vaccination significantly decreased the percentage of ALDH (high) cells in residual tumors. These data indicate that, when used in an adjuvant setting, ALDH (high) 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. This study has highlighted the potential application of cancer stem cell vaccine in the adjuvant setting.