A Biodegradable Antigen Nanocapsule Promotes Anti‐Tumor Immunity via the cGAS‐STING Pathway

Abstract Materials‐based antigen delivery systems can augment the immune response by improving antigen uptake in antigen‐presenting cells, targeting lymph nodes, prolonging antigen exposure, enhancing cross‐presentation, etc. Recent research revealed that some antigen carriers activate the innate immune pathways without additional adjuvant. Here, a vaccine delivery platform (antigen nanocapsules) constructed by a one‐step in situ polymerization is reported, weaving a biodegradable polymer network around the antigen surface. This simple technology allowed us to study the immunomodulatory effect of various antigen carriers. An antigen nanocapsule (NC7) capable of inducing dendritic cell activation and cross‐presentation is identified. Further mechanistic studies revealed that NC7 activated the cGAS‐STING pathway in a cGAS‐dependent manner. Moreover, the subcutaneously injected NC7 accumulated in the lymph nodes and elicited strong cytotoxic T cell immunity and T cell memory against established cancer. Collectively, the often‐neglected immunomodulatory effect of various cationic antigen carriers, enabling potential application in cancer vaccines, is uncovered.