Nanovaccine Based on Glycocalyx-Mimicking Nanovehicle to Potentiate the Immunogenicity of Neoantigen

Neoantigens are promising candidates for personalized cancer vaccines and immunotherapies. However, low immunogenicity and insufficient cross-presentation of neoantigens remain a major challenge. Inspired by natural glycocalyx and its important functions in immune response, here we report a glycocalyx-mimicking nanovehicle constructed from (oligo)mannoside-modified acid-sensitive glycopolymers to improve the efficiency of tumor neoantigens. These amphiphilic glycopolymers assembled into nanoparticles could serve as immune activators for dendritic cells maturation. The encapsulation of neoantigens in the glycopolymer nanocarrier improves the physicochemical properties and endosomal escape of the antigens, thereby not only enhancing their uptake and cross-presentation by dendritic cells but also promoting cytotoxic T cell proliferation and proinflammatory cytokine secretion. These results indicated that the glycocalyx-mimicking nanovehicle integrating delivery and immune adjuvant functions provides a promising platform for cancer vaccines.