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210 PD-1 blockade enhances anti-tumor effect induced by therapeutic HPV vaccine
  1. Jiae Kim and
  2. Dae Woo Lee
  1. Department of Obstetrics and Gynecology, St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon Si, South Korea


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

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