Metal-organic framework nanovaccines for systemic tumour regression.

Cancer vaccines can elicit antigen-specific antitumour immunity, but their clinical efficacy is often limited by their inability to sustain T-cell activation in tumours. Here we report MOF-Vac, a nanoscale metal-organic framework (MOF)-based therapeutic vaccine platform that co-delivers peptide antigens and STING agonists with high loading capacity and phosphate-triggered intracellular release. This design enables coordinated antigen presentation and innate immune activation, resulting in sustained T-cell priming and intratumoural effector function. In murine models of melanoma, colorectal cancer, triple-negative breast cancer, lung cancer and oropharyngeal cancer, MOF-Vac induced tumour regression, immune memory and protection against metastasis. MOF-Vac also synergized with radiotherapy and immune checkpoint blockade to eradicate both primary and distant tumours. Single-cell RNA sequencing and immune depletion studies revealed that therapeutic efficacy predominantly depends on macrophage-mediated antigen presentation and remodelling of the tumour microenvironment towards a proinflammatory, immune-active state. MOF-Vac provides a modular platform for off-the-shelf and personalized cancer vaccination.