The Antitumor Effect of a Non-transforming E7 Protein Combined with a TLR7 Agonist.

Abstract

Despite great efforts in developing peptide-based therapeutic vaccines against human papillomavirus (HPV)-induced cervical cancers, they have failed to elicit strong and sustainable immune responses. Here, we evaluated the vaccine potential of an HPV16 three mutant of E7 (E7GGG) (D21G/C24G/E26G) protein combined with Aldara (topical imiquimod) adjuvant in a TC-1 mouse tumor model. The HPV16-E7GGG, with eliminated transforming properties but retained antigenicity, and E7 wild-type were inserted into pET28, expressed in the E coli system, and purified using Ni-NTA chromatography. The E7GGG and E7 wild-type proteins were combined with Aldara adjuvant and injected into C57BL mice. We determined the ability of HPV16-E7GGG in combination with Aldara adjuvant to induce robust immune responses by IgG total development, IL-4, IL-17, and IFN-γ induction, CTL activity, and inhibit tumor growth in the murine TC-1 model in different immunized groups. The generated recombinant HPV16-E7GGG induced humoral and cellular immune responses in a TH1-mediated pathway, specifically with the (E7GGG) (D21G/C24G/E26G) antigen combined with Aldara, which could be a suitable therapeutic vaccine candidate against HPV.