Introduction/Background To demonstrate that blockade of inhibitory immune checkpoint, PD-1 pathway, is able to enhance the antitumor effects generated by therapeutic HPV vaccine, we tested the therapeutic HPV vaccines and in combination with programmed death- ligand 1 (PD-1) blockade in C57BL/6 mice with bearing the HPV16 E6/E7 transformed syngeneic tumor model, TC-1.

Methodology HPV16 E6E7-expressing TC-1 tumor was established in female C57BL/6 mice by injection of 1 × 105 of TC-1 cells subcutaneously. 3 days (estimate, needs to modify based on the tumor growth) later, two groups (5 mice/group) of mice were treated with 10 mg/kg of anti-mouse PD-1 monoclonal antibody (clone 29F.1A12) via intraperitoneal injection. When the tumor size demonstrated smaller from anti-PD-1 antibody treated mice than untreated mice, two groups (one group of untreated and one group of anti-PD-1 antibody treated) of TC-1 tumor-bearing mice were vaccinated with DDV regimen (pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine, TA-HPV).

Results Priming twice with an HPV DNA vaccine followed by a single TA-HPV booster immunization induced HPV-E6/E7 cell-mediated immunity and resulted in the clearance of small tumors and an overall survival benefit in mice with larger established tumors. When immunotherapy was combined with PD-1 immune checkpoint blockade, an increased level of anti-tumor activity against large tumors was observed in addition to an improvement in survival. Tumor microenvironment analysis in DDV and PD-1 blockade treated mice generated a comparable boost to E7-specific CD8+ T cell responses.

Conclusion Our results provide rationale for future clinical testing of HPV DNA vaccine prime, TA-HPV vaccinia vaccine boost immunization regimen with PD-1 blockade for the control of HPV-associated diseases

Disclosures None