Metalloimmunological hydrogel-based cancer vaccine potentiates postoperative tumor immunotherapy

Adjuvant immune checkpoint inhibitor (AICI) therapy is limited by inadequate durable immunological memory against tumor recurrence and metastasis. Herein, we present a metalloimmunological hydrogel-based and innate immunity-focused cancer vaccine (IT-Vax) that synergizes innate-adaptive crosstalk to potentiate AICI efficacy. Through systematic screening of 9 polysaccharide hydrogels with dual crosslinking (metal coordination/Schiff base), manganese-incorporated formulations demonstrate superior dendritic cell (DC) activation capacity through orchestrating innate immune pathways. The optimized IT-Vax, incorporating with a ROCK inhibitor and mitoxantrone-treated tumor cells functionally achieves five-pronged DC modulations: enhanced lymphatic migration, antigen presentation, costimulation, and priming of effector and memory T cells. Correspondingly, this multi-faceted activation translates in vivo into a marked accumulation of key DC subsets, including cDC1s and migratory DCs. Consequently, in therapeutic models, IT-Vax culminates in a robust cellular immune response, as attested by a 3.6-fold tumor growth suppression. Notably, in orthotopic breast cancer models, one-dose personalized IT-Vax combined with AICI therapy reduces postoperative metastasis by around 60% and extends median survival from 37 to over 100 days. This study establishes a personalized vaccine platform that mechanistically bridges innate immunostimulation with sustained adaptive memory, providing a strategy with translational potential to overcome the limitations of postoperative immunotherapy.