Tumor　neoantigen　peptide　vaccines　hold　potential　for　boosting　cancer　immunotherapy,　yet　efficiently　co-delivering　peptides　and　adjuvants　to　antigen-presenting　cells　in　vivo　remains　challenging.　Virus-like　particle　(VLP),　which　is　a　kind　of　multiprotein　structure　organized　as　virus,　can　deliver　therapeutic　substances　into　cells　and　stimulate　immune　response.　However,　the　weak　targeted　delivery　of　VLP　in　vivo　and　its　susceptibility　to　neutralization　by　antibodies　hinder　their　clinical　applications.　Here,　we　first　designed　a　novel　protein　carrier　using　the　mammalian-derived　capsid　protein　PEG10,　which　can　self-assemble　into　endogenous　VLP　(eVLP)　with　high　protein　loading　and　transfection　efficiency.　Then,　an　engineered　tumor　vaccine,　named　ePAC,　was　developed　by　packaging　genetically　encoded　neoantigen　into　eVLP　with　further　modification　of　CpG-ODN　on　its　surface　to　serve　as　an　adjuvant　and　targeting　unit　to　dendritic　cells　(DCs).　Significantly,　ePAC　can　efficiently　target　and　transport　neoantigens　to　DCs,　and　promote　DCs　maturation　to　induce　neoantigen-specific　T　cells.　Moreover,　in　mouse　orthotopic　liver　cancer　and　humanized　mouse　tumor　models,　ePAC　combined　with　anti-TIM-3　exhibited　remarkable　antitumor　efficacy.　Overall,　these　results　support　that　ePAC　could　be　safely　utilized　as　cancer　vaccines　for　antitumor　therapy,　showing　significant　potential　for　clinical　translation.　©　2024,　Tang,　Guo　et　al.