857 Development of an mRNA cancer vaccine platform enabling flexible antigen exchange and dendritic cell selected delivery to overcome immune tolerance
Year: 2026
Type: conference-abstract
Abstract: Background mRNA cancer vaccines are advancing in both personalized neoantigen and fixed-antigen settings, yet their clinical efficacy remains limited by inefficient in vivo delivery to professional antigen-presenting cells and insufficient immune activation. These challenges are particularly pronounced for tumor-associated self-antigens, where immune tolerance restricts effective T cell responses. In parallel, current platforms require antigen-specific reformulation, limiting applicability to rapid and scalable personalized vaccine workflows. To address these challenges, we developed NanoReady, a premanufactured RNA-free platform that enables modular loading of diverse mRNA antigens, promotes efficient immune activation, and overcomes immune tolerance.Methods Pre-assembled, RNA-free NanoReady were prepared and combined with antigen-encoding mRNA by simple mixing before administration. To determine whether the platform delivered mRNA to tissues and cell populations involved in T-cell priming, tissue distribution, cellular uptake, and protein expression were evaluated following intravenous administration, with particular emphasis on the spleen and dendritic cells. To evaluate whether the platform could induce robust T-cell immunity across different antigen classes, we tested it using a foreign antigen (OVA), Tumor-associated self-antigen (mTrp2), and neoantigens. T-cell responses against the Tumor-associated self-antigen (rhTERT) were further evaluated in NHPs. Repeat-dose compatibility was assessed through iterative immunization, with booster responses and systemic toxicity monitored after repeated administration.Results Upon simple mixing, preassembled RNA-free NanoReady efficiently incorporated diverse antigen-encoding mRNAs, forming stable multilamellar nanoparticles that encapsulated approximately 700 mRNA molecules per particle. Following administration, NanoReady-mRNA achieved spleen-selective biodistribution in mice and NHPs, with preferential protein expression in dendritic cells observed in mice. NanoReady elicited robust antigen-specific T-cell responses against the OVA and B16-F10 neoantigens. Importantly, it overcame immune tolerance and induced robust T-cell responses against the tumor-associated self-antigen (mTrp2) in mice. In NHPs, NanoReady loaded with rhTERT mRNA elicited potent rhTERT-specific T-cell responses, demonstrating potent T-cell immunogenicity in a translationally relevant model. Functionally, NanoReady-mTrp2 mRNA significantly suppressed tumor growth and improved survival in a B16-F10 melanoma model. Comparative evaluation across neoantigen-, TAA-, and combination-targeting mRNA vaccines supports the potential of multi-antigen targeting strategies to enhance antitumor efficacy.Conclusions The NanoReady platform decouples antigen design from delivery, enabling rapid mRNA payload exchange. Its spleen-selective, dendritic cell–focused delivery elicited T-cell immunity across foreign, tumor-associated self-, and neoantigens and overcame self-tolerance, supporting both personalized and fixed-antigen mRNA cancer vaccines.
Authors: Sojin Lee, So-Young Kim, Helen Cho
Institution: Samyang Holdings (South Korea)
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225143008