Cytosolic Delivery of Thiolated Neoantigen Nano-Vaccine Combined with Immune Checkpoint Blockade to Boost Anti-Cancer T Cell Immunity.

ABSTRACT: Although tumor-specific neoantigen-based cancer vaccines hold tremendous potential, it still faces low cross-presentation associated with severe degradation via endocytosis pathway. Herein, a thiolated nano-vaccine allowing direct cytosolic delivery of neoantigen and Toll like receptor 9 agonist CpG-ODN is developed. This approach is capable of bypassing the endo-/lysosome degradation, increasing uptake and local concentration of neoantigen and CpG-ODN to activate antigen-presenting cells, significantly strengthening the anti-cancer T-cell immunity. In vivo immunization with thiolated nano-vaccine enhanced the lymph organ homing and promoted the antigen presentation on dendritic cells, effectively inhibited tumor growth, and significantly prolonged the survival of H22-bearing mice. Strikin

SUBMITTER: Zhang D 

PROVIDER: S-EPMC7967047 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature