Enhanced Cancer DNA Vaccine <i>via</i> Direct Transfection to Host Dendritic Cells Recruited in Injectable Scaffolds.

Abstract

Deoxyribonucleic acid (DNA) vaccines are a promising cancer immunotherapy approach. However, effective delivery of DNA to antigen-presenting cells (<i>e</i>.<i>g</i>., dendritic cells (DCs)) for the induction of an adaptive immune response is limited. Conventional DNA delivery <i>via</i> intramuscular, intradermal, and subcutaneous injection by hypodermal needles shows a low potency and immunogenicity. Here, we propose the enhanced cancer DNA vaccine by direct transfection to the high number of DCs recruited into the chemoattractant-loaded injectable mesoporous silica microrods (MSRs). Subcutaneous administration of the MSRs mixed with tumor-antigen coding DNA polyplexes resulted in DC recruitment in the macroporous space of the scaffold formed by the spontaneous assembly of high-aspect-ratio MSRs, thereby allowing for enhanced cellular uptake of antigen-coded DNA by host DCs. The MSR scaffolds delivering the DNA vaccine trigger a more robust DC activation, antigen-specific CD8⁺ T cell response, and Th1 immune response compared to the bolus DNA vaccine. Additionally, the immunological memory can be induced with a single administration of the vaccine. The combination of the vaccination and antiprogrammed cell death-1 antibody significantly eliminates established lung metastasis. These results indicate that MSRs serve as a powerful platform for DNA vaccine delivery to DCs for effective cancer immunotherapy.