Harnessing enucleated cancer cells as Trojan horse cell vaccines

Inactivated tumor cells preserve a whole spectrum of tumor antigens, including neoantigens that can elicit potent immune response. Nevertheless, avoiding tumorigenic risks while stimulating a robust anti-tumor immune response remains a pivotal challenge. Herein, we prepare enucleated cancer cells decorated with bacteria-derived vesicles (BDVs) carrying stimulator of interferon gene (STING) agonists as live cell vaccines. Enucleated cancer cells retain intact cell morphology excepting the nucleus. BDVs loaded with STING agonist cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) are further conjugated to enucleated cancer cells to potentiate immunogenicity. Subcutaneous enucleated cancer cell-BDV-cGAMP vaccine inoculation effectively recruits and incents dendritic cells and macrophages to capture tumor antigens. Moreover, combining with anti-programmed cell death 1 antibodies further enhances M1 macrophage polarization, promoting tumor-specific T cell infiltration. Additionally, the live cell vaccines foster CD44+ CD62L− effector memory T cell and TCF1+ CD8+ stem cell-like memory T cell formation, which contribute to impeding melanoma progression and metastasis.