Anti-tumor efficacy and immune responses induced by a novel therapeutic HPV-specific gorilla adenovirus off-the-shelf immunotherapeutic (PRGN-2009)

Abstract

Abstract There are about 44,000 cases of Human Papilloma Virus (HPV) associated cancer each year in the US, most commonly caused by HPV 16 and 18. Prophylactic vaccines have been successful at preventing healthy patients from acquiring HPV infections via the induction of HPV specific antibodies. To treat established HPV-associated malignancies, however, the continued development of new therapies is necessary. One promising new modality is HPV immunotherapeutics, which target the HPV 16 and 18 oncoproteins E6 and E7 with the goal to activate antigen specific cytotoxic T cells. Here, we evaluated PRGN-2009, a novel gorilla adenovirus GAd HPV off-the-shelf immunotherapeutic containing multiple CTL agonist epitopes of E6 and E7 to enhance the immune responses. Three weekly administrations with PRGN-2009 in the TC-1 mouse model led to decreases in tumor volume and weight, and significant increases in HPV16 E6-specific splenocytes evaluated by IFNg ELISPOT. PRGN-2009 also increased the tumor-infiltrating CD8 and CD4 T cells, as well as multi-functional (IFNg+, GzmB+) CD8 T cells in the tumor microenvironment (TME). Additionally, PRGN-2009 was tested in SiHa, a human HPV16+ cervical tumor, in the NSG β2m−/− PBMC humanized mouse model. Weekly PRGN-2009 administrations led to a reduction in tumor and a trending increase in CD8 and CD4 T cells in the tumor; IHC confirmed the increase of CD8 T cells into the TME. These studies provide the first evaluation of the GAd HPV off-the-shelf immunotherapeutic PRGN-2009 and its therapeutic impact against HPV-associated cancers.