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

Abstract

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 (αCD40) 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 (α4-1BB) 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. STATEMENT OF SIGNIFICANCE: 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 the antitumor immunity of subunit vaccines, we develop novel vaccine formulations that integrate multifunctional modalities including (1) a nano-adjuvant containing anti-CD40 monoclonal antibody (αCD40) and TLR3 agonist which activate innate immunity through diverse signaling pathways, (2) a peptide amphiphile containing an optimized CD8+ T-cell epitope from tumor antigen, (3) an anti-4-1BB monoclonal antibody (α4-1BB) that boosts the efficacy of vaccinations. In this study, our vaccine formulations stimulate superior antitumor immunity and control tumor progression. The above nano-engineered platform and immunogenic biomacromolecules can be further applied to other T-cell-inducing vaccines.