TY - JOUR AU - Pellom, Samuel T. AU - Smalley Rumfield, Claire AU - Morillon, Y. Maurice, II AU - Roller, Nicholas AU - Poppe, Lisa K. AU - Brough, Douglas E. AU - Sabzevari, Helen AU - Schlom, Jeffrey AU - Jochems, Caroline T1 - Characterization of recombinant gorilla adenovirus HPV therapeutic vaccine PRGN-2009 PY - 2021/04/08/ AB - There are approximately 44,000 cases of human papillomavirus–associated (HPV-associated) cancer each year in the United States, most commonly caused by HPV types 16 and 18. Prophylactic vaccines successfully prevent healthy people from acquiring HPV infections via HPV-specific antibodies. In order to treat established HPV-associated malignancies, however, new therapies are necessary. Multiple recombinant gorilla adenovirus HPV vaccine constructs were evaluated in NSG-β2m–/– peripheral blood mononuclear cell–humanized mice bearing SiHa, a human HPV16+ cervical tumor, and/or in the syngeneic HPV16+ TC-1 model. PRGN-2009 is a therapeutic gorilla adenovirus HPV vaccine containing multiple cytotoxic T cell epitopes of the viral oncoproteins HPV 16/18 E6 and E7, including T cell enhancer agonist epitopes. PRGN-2009 treatment reduced tumor volume and increased CD8+ and CD4+ T cells in the tumor microenvironment of humanized mice bearing the human cervical tumor SiHa. PRGN-2009 monotherapy in the syngeneic TC-1 model also reduced tumor volumes and weights, generated high levels of HPV16 E6–specific T cells, and increased multifunctional CD8+ and CD4+ T cells in the tumor microenvironment. These studies provide the first evaluation to our knowledge of a therapeutic gorilla adenovirus HPV vaccine, PRGN-2009, showing promising preclinical antitumor efficacy and induction of HPV-specific T cells, along with the rationale for its evaluation in clinical trials. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.141912 VL - 6 IS - 7 UR - https://doi.org/10.1172/jci.insight.141912 PB - The American Society for Clinical Investigation ER -