Inhibition of Orthotopic Genital Cancer Induced by Subcutaneous Administration of Human Papillomavirus Peptide Vaccine with CpG Oligodeoxynucleotides as an Adjuvant in Mice.

Abstract

PurposePersistent high-risk human papillomavirus (HPV) infection is the most common cause of cervical cancer and its precursor lesions. Although prophylactic HPV vaccines have been applied in the general population for the prevention of HPV infections, no licensed therapeutic HPV vaccine is currently available to treat preexisting HPV infections or HPV-associated diseases, including cervical cancer.Materials and MethodsThe most common murine cervical cancer model used for the evaluation of the efficacy of a therapeutic HPV vaccine in preclinical studies is the ectopic model, which is established by the subcutaneous inoculation of tumor cells, such as TC-1 cells, into the flank of an animal. We have previously demonstrated the efficacy of a therapeutic HPV peptide vaccine adjuvanted with unmethylated cytosine-phosphate-guanosine oligodeoxynucleotide in the clearance of ectopic subcutaneous tumors in C57BL/6 mice after vaccination. In the current study, we established orthotopic genital tumors by injecting TC-1 cells into the vaginal submucosa close to the cervix and assessed whether the subcutaneous administration of the therapeutic vaccine could inhibit the growth of genital tumors. Additionally, we evaluated the effect of the vaccination on the tumor microenvironment.ResultsThe results showed that the vaccination induced an increase in infiltrating CD4+ and CD8+ T cells, a decrease in myeloid-derived suppressor cells and cancer-associated fibroblasts, as well as the differential expression of a panel of cytokines, chemokines, and matrix metalloproteinases within the tumor microenvironment.ConclusionThe administration of the vaccine resulted in the inhibition of established implanted orthotopic genital tumors by inducing strong antitumor immune responses and reversed tolerogenic local immunosuppression in a mouse model of orthotopic genital cancer.