Immune Adjuvant Targeting Micelles Allow Efficient Dendritic Cell Migration to Lymph Nodes for Enhanced Cellular Immunity.

Abstract

Cellular immunity is essential for the effectiveness of vaccines against cancer. After capture of vaccines, dendritic cells (DCs) have to migrate to lymph nodes via chemokine receptor type 7 (CCR7). Subsequently, DCs present cytosolic antigens via major histocompatibility complex class I (MHC I) molecules to induce cellular immunity. However, various vaccines fail to induce potent cellular immunity due to insufficient MHC I-restricted antigen presentation and limitations of immune adjuvants. Hence, we constructed novel immune adjuvant targeting micelles (M-COSA) to targeted codeliver antigen ovalbumin (OVA) and plasmid DNA encoding CCR7 (CCR7 pDNA) to the cytosol of DCs, thus promoting DC migration to lymph nodes to boost MHC I-restricted antigen presentation. M-COSA exhibited adjuvant activity and demonstrated more efficient DC cellular uptake compared with COSA. M-COSA/OVA/pDNA increased costimulatory molecule expression and cytokine secretion, resulting in DC activation and maturation. Moreover, antigens and pDNA, which were encapsulated in micelles, escaped from the endosome into the cytoplasm to achieve MHC I-restricted antigen presentation and increase CCR7 expression. The number of CD8+ T cells, which was positively correlated with tumor rejection, was notably increased and tumor growth was dramatically suppressed after vaccination with M-COSA/OVA/pDNA. In summary, M-COSA/OVA/pDNA micelles, which allow DC targeting and efficient DC migration to lymph nodes to enhance cellular immunity, exhibit effective tumor inhibition and lay the foundation for novel vaccine design.