Combination of Vaccine With IL‐12‐Armed Oncolytic Virus SKV‐012 Synergistically Potentiates Immune Responses in HPV‐Associated Malignancies

ABSTRACT Currently, patients with advanced‐stage or refractory human papillomavirus (HPV)‐associated malignancies have few therapeutic options. Despite therapeutic HPV vaccines having been investigated, the lack of appreciable efficacy highlights the urgent need to develop more effective strategies. Here, we developed an immuno‐oncotherapy for HPV‐induced tumors based on an adenoviral (Ad)‐vectored therapeutic vaccine that contains concatemeric T cell epitopes, and evaluated oncolytic viruses (OV) as potential approach to enhance vaccine efficacy. We observed that the therapeutic vaccine encoding the HPV E7 oncoprotein epitope (Ad‐E7P) significantly inhibited tumor growth in HPV‐induced murine models by inducing systemic antitumor CD8+T cell responses and promoting the formation of tertiary lymphoid structures in peritumoral regions. We then evaluated the potential of combining the vaccine with an interleukin‐12 (IL‐12)–armed oncolytic herpesvirus (SKV‐012) in preclinical models. The combination therapy elicited potent antitumor responses by inducing antigen‐specific T‐cell expansion, remodeling the tumor microenvironment, and generating immune memory, which led to tumor clearance. Overall, these findings support that the vaccine synergizes with the OV as an effective approach to enhance antitumor immunity in HPV‐associated malignancies.