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

摘要

Materials-based antigen delivery systems can augment the immune responseby improving antigen uptake in antigen-presenting cells, targeting lymphnodes, prolonging antigen exposure, enhancing cross-presentation, etc.Recent research revealed that some antigen carriers activate the innateimmune pathways without additional adjuvant. Here, a vaccine delivery platform(antigen nanocapsules) constructed by a one-step in situ polymerizationis reported, weaving a biodegradable polymer network around the antigensurface. This simple technology allowed us to study the immunomodulatoryeffect of various antigen carriers. An antigen nanocapsule (NC7) capable ofinducing dendritic cell activation and cross-presentation is identified. Furthermechanistic studies revealed that NC7 activated the cGAS-STING pathway ina cGAS-dependent manner. Moreover, the subcutaneously injected NC7 accumulatedin the lymph nodes and elicited strong cytotoxic T cell immunity andT cell memory against established cancer. Collectively, the often-neglectedimmunomodulatory effect of various cationic antigen carriers, enablingpotential application in cancer vaccines, is uncovered.