Abstract 2866: Neoantigen nanovaccine improves personalized cancer immunotherapy

Background: Neoantigens are attractive targets for personalized anti-tumor vaccination, given their uniqueness to the tumor and the ability to bypass immune tolerance. Recently, the feasibility of neoantigen vaccine has been demonstrated in patients. However, the response rate of neoantigen vaccines is unsatisfied because of their low immunogenicity, undesired degradation, limited cross-presentation, and acquired resistance. Here, we developed a nanoparticle-based neoantigen vaccine system to overcome these challenges. Methods: We predicted both MHC Class I and Class II neoantigen peptides for B16-F10 melanoma model using a bioinformatics pipeline. We screened an optimal incorporation strategy to formulate nanovaccines by either directly absorbing neoantigen peptides on PLGA nanoparticle (NP) or conjugating them to PEG-PLGA through a pH-responsive strategy or a redox-responsive strategy. We formulated nanovaccine with redox-responsive neoantigen-polymer conjugates and a STING agonist DMXAA. C57/BL6 mice were inoculated with 50,000 B16-F10 tumor cells on their right flank. Mice were vaccinated subcutaneously on their left flank with different nanovaccines or control arms on day 4, 8 and 12 after tumor inoculation. Mice were given anti-PD1 (200 μg, intraperitoneally) on day 4, 8, 12, 16, 20 after tumor inoculation. Tumor volume and mice survival were recorded. We also evaluated the immune related cytokines in mouse blood on day 15 after treatment. Results: Four MHC I and three MHC II neoantigen peptides were screened out for B16-F10 melanoma with high IFN-γ immune response. Results indicate that a redox conjugation strategy using PLGA-PEG and SPDP linker were more efficient in tumor inhibition than other incorporation strategies for our neoantigen peptides. By formulating nanovaccine with redox-responsive neoantigen-polymer conjugates and a STING agonist, we demonstrated that our nanovaccine, when combined with αPD1, achieved a 50% survival rate on day 38, compared to 0% of PBS treated group and 20% of non-formulated neoantigen peptides treated group. To confirm the enhanced immunity, we evaluated the immune related cytokines in mouse blood on day 15 after treatment. We found that our neoantigen nanovaccine achieved the highest expression of immune related cytokines among all arms, indicating that our nanovaccine induced higher immune response than non-formulated neoantigen peptides or other NP strategies. Conclusions: We demonstrate that our nanovaccine achieves increased therapeutic efficacy and higher expression of immune related cytokines than non-formulated neoantigen peptides. Our work develops a novel nanoparticle-based neoantigen vaccine that will improve current personalized cancer immunotherapy. Citation Format: Yu Mi, Christof C. Smith, Jonathan S. Serody, Benjamin G. Vincent, Andrew Z. Wang, Hyesun Hyun. Neoantigen nanovaccine improves personalized cancer immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2866.