Metal‐Phenolic Nanocloaks on Cancer Cells Potentiate STING Pathway Activation for Synergistic Cancer Immunotherapy

Due to the presence of natural neoantigens, autologous tumor cells hold great promise as personalized therapeutic vaccines. Yet autologous tumor cell vaccines require multi‐step production that frequently leads to the loss of immunoreactive antigens, causing insufficient immune activation and significantly hampering their clinical applications. Herein, we introduce a novel whole‐cell cancer vaccine by cloaking cancer cells with lipopolysaccharide‐decorated manganese(II)‐phenolic networks (MnTA nanocloaks) to evoke tumor‐specific immune response for highly efficacious synergistic cancer immunotherapy. The natural polyphenols coordinate with Mn2+ and immediately adhere to the surface of individual cancer cells, thereby forming a nanocloak and encapsulating tumor neoantigens. Subsequent decoration with lipopolysaccharide induces internalization by dendritic cells, where Mn2+ ions are released in the cytosol, further facilitating the activation of the stimulator of the interferon genes (STING) pathway. Highly effective tumor suppression was observed by combining the nanocloaked cancer cell treatment with anti‐programmed cell death ligand 1 (anti‐PD‐L1) antibodies‐mediated immune checkpoint blockade therapy. Our work demonstrates a universal yet simple strategy to engineer a cell‐based nanobiohybrid system for enhanced cancer immunotherapy. A biohybrid system (LMP vaccine) that is based on living cancer cells and a manganese‐phenolic nanocloak is developed for synergistic immunotherapy. The nanocloak affords an immunoactive exoskeleton by integrating the toll‐like receptor ligand to enhance dendritic cell engulfment and Mn2+ ions to sensitize the stimulator of the interferon genes (STING) pathway, leading to superior therapeutic efficacy against melanoma.