(676d) DNA-Launched HPV E7 Nanoparticle Vaccine Achieves Long-Term Protection Against Tumor Challenge In Vivo

HPV-induced cancers constitute a pressing global public health issue, accounting for over 600,000 cases per year worldwide. By age 50, more than 80% of all individuals have been exposed to HPV infection. Prophylactic vaccines developed in recent years are reducing new HPV infections, but current vaccine formulations fail to induce the cellular immunity necessary to address those with already established HPV infections or malignancies. Nanotechnology-based approaches have provided promising new strategies in anti-cancer immunotherapeutic vaccines through the decoration of multiple immunogens on nanoparticle scaffolds; however, their clinical translation have been hampered by challenges with scalability and purification. To address these challenges, here we present the design and characterization of a novel DNA-encoded nanoparticle vaccine (DNP) scaffolding HPV E7 HLA-Kb epitope with lumazine synthase for inducing anti-tumor immune responses. We demonstrate that through electroporation-facilitated intramuscular DNA vaccination, the scaffolded peptide is produced and self-assembles in vivo into 60-mer nanoparticles. Compared to CpG-adjuvanted peptide vaccines, the DNP induced significantly greater antigen-specific CD8+ T cell responses. This translated into tumor protection in 100% of mice when administered prophylactically and complete tumor regression in 50% of mice upon therapeutic treatment in a flank tumor model of HPV-induced cancer. Anti-tumor immunity was retained upon rechallenge over 150 days after initial tumor challenge, supporting the induction of potent immune memory. Finally, in a metastatic lung tumor model, DNP treatment demonstrated prolonged survival and significantly improved lung pathology compared to the CpG-adjuvanted peptide vaccine. These promising results, along with its facile characterization and scalability, support DNA-launched nanovaccines as a promising new platform for inducing potent anti-tumor cellular immunity ideally positioned for study in clinical translation.