Histone deacetylase inhibitor AR-42 enhances E7-specific CD8+ T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination

We have previously created a potent DNA vaccine encoding calreticulin linked to the human papillomavirus (HPV) oncogenic protein E7 (CRT/E7). While treatment with the CRT/E7 DNA vaccine generates significant tumor-specific immune responses in vaccinated mice, the potency with the DNA vaccine could potentially be improved by co-administration of a histone deacetylase inhibitor (HDACi) as HDACi has been shown to increase the expression of MHC class I and II molecules. Thus, we aimed to determine whether coadministration of a novel HDACi, AR-42, with therapeutic HPV DNA vaccines could improve the activation of HPV antigen-specific CD8 + T cells, resulting in potent therapeutic antitumor effects. To do so, HPV-16 E7-expressing murine