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However, delivery of neoantigen peptide vaccines to antigen\u2010presenting cells (APCs) at these sites remains challenging. In this study, LNPs<jats:sup>D18<\/jats:sup>, a cationic liposomal formulation that targets and enhances APC uptake at both sites without modifying the targeting ligands is developed. By co\u2010delivering tumor\u2010specific neoantigens and a cholesterol\u2010coupled toll\u2010like receptor 9 (TLR9) agonist within LNP\u2010vax<jats:sup>D18<\/jats:sup>, an approximately 60\u2010fold increase in dendritic cell uptake compared to neoantigen\u2010adjuvant mixtures is achieved. Intravenous administration of the liposome\u2010neoantigen peptide vaccine targets both the spleen and the tumor, boosting splenic DC activation, increasing M1\u2010type tumor\u2010associated macrophages, and elevating tumor cytokine levels. 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