Coinjection of IL2 DNA enhances E7-specific antitumor immunity elicited by intravaginal therapeutic HPV DNA vaccination with electroporation

The generation and use of therapeutic human papillomavirus (HPV) DNA vaccines represent an appealing treatment method against HPV-associated cervical cancer due to their safety and durability. Previously, we created a therapeutic HPV DNA vaccine candidate by linking the HPV16-E7 DNA sequence to calreticulin (CRT/E7), which we showed could generate significant E7-specific cytotoxic T lymphocyte (CTL)-mediated anti-tumor immune responses against HPV16 oncogenes expressing murine tumor model TC-1. Here we assess the therapeutic efficacy of intravaginal immunization with pcDNA3-CRT/E7 followed by electroporation. In addition, we examined whether coadministration of DNA encoding IL2 with the pcDNA3-CRT/E7 could improve the T cell responses elicited by pcDNA3-CRT/E7. TC-1 tumor-bearing mice vaccinated intravaginally with both pcDNA3-CRT/E7 and IL2 DNA followed by electroporation induced stronger local anti-tumor CTL response in comparison to mice that received other treatment regimens. Additionally, we found that coadministration of IL2 DNA with pcDNA3-CRT/E7 modified the tumor microenvironment by decreasing the population of regulatory T cells and myeloid derived suppressor cells relative to that of CTLs. Our data demonstrates the translational potential of local administration of IL2 and pcDNA3-CRT/E7 followed by electroporation in treating cervicovaginal tumors.