Pharmacologically modified pluripotent stem cell-based cancer vaccines with anti-metastatic potential

Abstract

Cancer is maintained by the activity of a rare population of self-renewing "cancer stem cells" (CSCs), which are resistant to conventional therapies. CSCs share several antigenic determinants with pluripotent stem cells (PSCs). We show here that PSCs, combined with a histone deacetylase inhibitor (HDACi), are able to elicit major anti-tumor responses in a model of highly aggressive breast cancer. This immunotherapy strategy was effective in preventing tumor establishment and efficiently targeted CSCs by inducing extensive modifications of the tumor microenvironment. The anti-tumor effect was correlated with a reduction in regulatory T and myeloid-derived suppressor cell populations and an increase in cytotoxic CD8+T cells within the tumor and the spleen along with a drastic reduction in metastatic dissemination and an improvement in the survival rate. These results demonstrate for the first time the possibility of using PSCs and HDACi as an allogeneic anticancer vaccine, in future universal immunotherapy strategies.