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  • Poster presentation
  • Open Access

An HPV-E6/E7 immunotherapy plus PD-1 checkpoint inhibition results in tumor regression and reduction in PD-L1 expression

  • 1,
  • 1,
  • 1,
  • 2,
  • 1 and
  • 1
Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P449

https://doi.org/10.1186/2051-1426-3-S2-P449

  • Published:

Keywords

  • Squamous Cell Carcinoma
  • Human Papilloma Virus
  • Neck Squamous Cell Carcinoma
  • Immune Checkpoint
  • Future Clinical Trial

The prevalence of head and neck cancers in the USA is estimated to be about 370,000 and between 25% to 38% of these are human papilloma virus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). We have developed a viral gene delivery platform to immunize against HPV 16 genes E6 and E7 (Ad5 [E1-, E2b-]-E6/E7) for the treatment of HPV-associated HNSCC. We tested the Ad5 [E1-, E2b-]-E6/E7 immunotherapy alone and in combination with programmed death-ligand 1 (PD-1) blockade in a murine HPV+ tumor model. As a single agent, Ad5 [E1-, E2b-]-E6/E7 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 Ad5 [E1-, E2b-]-E6/E7 treated mice revealed an increase in CD8+ tumor-infiltrating lymphocytes (TILs). In addition, we observed induction of suppressive mechanisms such as programmed death-ligand 1 (PD-L1) expression on tumor cells and an increase in PD-1+ TILs. When Ad5 [E1-, E2b-]-E6/E7 immunotherapy was combined with anti-PD-1 antibody, we observed CD8+ TILs at the same increased level but found that a smaller fraction of these were PD-1+. Furthermore, we observed a reduction in PD-L1 expression on tumor cells, providing a mechanism by which combination therapy favors tumor clearance and a rationale for pairing antigen-specific vaccines with checkpoint inhibitors in future clinical trials.

Authors’ Affiliations

(1)
Etubics Corporation, Seattle, WA, USA
(2)
Sanford Cancer Research Center, University of South Dakota Medical School, Sioux Falls, SD, USA

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