Nano-adjuvants and immune agonists promote antitumor immunity of peptide amphiphiles

摘要

Immunostimulatory cues play an important role in priming antitumor immunity and promoting the efficacy of subunit cancer vaccines. However, the clinical use of many immunostimulatory agents is often hampered by their inefficient in vivo delivery which may decrease immune response to the vaccination. To promote vaccine efficacy, we develop vaccine formulations which integrate three key elements: (1) a nano-adjuvant formulated by conjugating an agonistic anti-CD40 monoclonal antibody ( alpha CD40) to the surface of a polyIC-loaded lipid nanoparticle, (2) a peptide amphiphile containing an optimized CD8 + T-cell epitope that derived from a melanoma antigen gp100, (3) an agonistic anti-4-1BB monoclonal antibody ( alpha 4-1BB) that boosts the efficacy of vaccinations. In a syngeneic mouse model of melanoma, the vaccine formulations enhanced innate immunity and activated multiple innate immune signaling pathways within draining lymph nodes, as well as promoted antigen-specific immune responses and reduced immunosuppression in the tumor microenvironment, leading to profound tumor growth inhibition and prolonged survival. Thus, our vaccine formulations represent an attractive strategy to stimulate antitumor immunity and control tumor progression.

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