Abstract 2011: Polycondensate-epitope vaccine augments anti-cancer T lymphocyte responses and induces long-term immune memory

Abstract

Abstract Background: Personalized cancer vaccines are promising treatments to induce or augment antitumor responses. Despite the observed benefits in early-phase clinical studies, the clinical efficacy of cancer vaccines remains modest. Here, we aim to develop a vaccine delivery strategy to enhance the antitumor efficacy of cancer vaccines. Method: We developed polycondensate-epitope vaccines (PEVs) for co-delivering of major histocompatibility complex (MHC) I and II-restricted peptides (OVA257-264 and OVA323-339) to elicit antigen-specific CD4+ and CD8+ T cells for long-term antitumor immunity. PEVs were prepared by polymerizing amino-functionalized MHC I and MHC II-restricted peptides with a TLR1/2 agonist, Pam3CSK4, using a responsive linker. We characterized the physical properties (size, MW) and responsiveness of the prepared PEVs. The immunogenicity was evaluated in mice via flow cytometry and ELISpot assay. We finally assessed the antitumor efficacy in both prophylactic and therapeutic tumor models. Results: The prepared PEVs have an average size of 20 nm to 50 nm, >95% incorporating efficiency, and a remarkably high loading capacity of antigens and adjuvants (57.18~ 61.3 wt/wt %). PEVs consisting of both MHC I and MHC II-restricted OVA peptides induced robust antigen-specific CD4+ and CD8+ T cell responses and long-term memory immune response against tumors. The vaccine-induced CD8+ and CD4+ T cells exhibited high proliferative capacity and polyfunctionality upon antigen restimulation ex vivo. In a prophylactic model, mice immunized by PEVs completely rejected the first and the second challenge of YUMM1.7-OVA tumor cells with 100% rejection rate. In a therapeutic model, treatment with PEVs loaded OVA257-264 and OVA323-339 peptides induced marked tumor regression in mice bearing established YUMM1.7-OVA tumors showing enhanced anti-tumor efficacy as compared to PEVs loaded with CD8 epitope alone. Conclusion: Our results demonstrate that PEV is a promising vaccine delivery strategy for eliciting highly effective and durable anti-cancer immune responses. Citation Format: Xiaomeng Hu, Li Tang. Polycondensate-epitope vaccine augments anti-cancer T lymphocyte responses and induces long-term immune memory [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2011.