Abstract 1738: DNA-launched nanoparticle vaccines induce cytolytic T cell responses for in vivo tumor control

Abstract Nanotechnology-based approaches have achieved promising results for the development of novel immunotherapeutic cancer vaccines through the decoration of antigens on nanoparticle scaffolds for multivalent display. However, their translation have been limited due to challenges with purification, scalability, and robust induction of cytolytic T cell responses critical to anti-tumor activity. We designed a nanovaccine construct by fusing the HPV E7 immunodominant epitope onto lumazine synthase scaffold. We demonstrate that through electroporation-facilitated DNA delivery encoding the antigen-scaffold construct, this nanovaccine is expressed and self-assembles in vivo into 60-mer nanoparticles. Compared to CpG-adjuvanted peptide and monomeric DNA vaccination, this DNA-launched nanovaccine induced greater CD8+ cellular responses against the E7 epitope and target tumor cells. In both flank and lung models of TC-1 HPV-associated cancers, the nanovaccine achieved significant tumor regression and prolonged survival compared to CpG-adjuvanted peptide. Anti-tumor immunity was retained upon rechallenge >150 days after initial challenge, supporting the induction of long-term immune memory. In addition, we demonstrate that this DNA-launched nanovaccine platform can be used to form hybrid nanoparticles displaying multiple antigens simultaneously. These hybrid nanoparticles exhibit synergistic efficacy, with improved tumor control over administration of separate single-antigen nanovaccines. These promising results, along with facile characterization, scalability, and stability, support that DNA-launched nanovaccines can induce potent anti-tumor cellular immunity and are ideally positioned for further translational development for clinical evaluation. Citation Format: Kevin Liaw, Ziyang Xu, Neethu Chokkalingam, Daniel Kulp, David Weiner. DNA-launched nanoparticle vaccines induce cytolytic T cell responses for in vivo tumor control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1738.