Abstract 5007: Ex vivo evaluation of mRNA lipid nanoparticle cancer vaccines

Abstract

Abstract Lipid nanoparticle vaccines have recently been developed broadly against pathogens and recently, in precision medicine targeting mutations in different tumors. Evaluating vaccine candidates typically require animal models using orthotopic or allogenic transplantations to evaluate efficiency. Evaluating vaccine efficacy using ex vivo systems is faster and less technically demanding. Here we aim to develop individualized cancer vaccines based on neoantigen identified within established human organoids or directly from patient tissue. The selected neoantigens are enriched for epitopes identified on gene fusions. Identified gene fusions encoding predicted immunogenic proteins are inserted into a vaccine backbone and used to make mRNA lipid nanoparticle vaccines. The neoantigen candidates are then evaluated in a personalized ex vivo testbed. Within the ex vivo testbed personal tumor neoantigens are tested on the patients own isolated CD8+ T cells and monocytes. Monocytes are in vitro differentiated into monocyte derived dendritic cells (moDCs), which specialize in antigen cross presentation. The moDCs are inoculated with mRNA lipid nanoparticle vaccines or loaded with peptides. The moDCs are then co-cultured with syngeneic T cells. Vaccine candidates are evaluated based on CD8+ T cell activation and cytotoxicity in the co-culture ex vivo testbed. Our pipeline offers a fast and efficient means of evaluating individualized vaccine candidates. Effective vaccines developed through this process can be administered as a standalone therapy or in combination with checkpoint inhibitors, to generate a strong durable immune response against a variety of solid tumor types. Citation Format: Tommy Lidström, Mara Blanco Arauzo, Nickolas Karlowatz, Mikael Johansson, Mattias Forsell, Jonas Nilsson. Ex vivo evaluation of mRNA lipid nanoparticle cancer vaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5007.