Dendritic Cell Derived-Extracellular Vesicles Engineered to Express Interleukin-12 and Anti-CTLA-4 on Their Surface for Combinational Cancer Immunotherapy.

ABSTRACT: Dendritic cell (DC)-derived extracellular vesicles (DEVs) are promising candidates for cancer vaccines, but their therapeutic effects still need further optimization. In this study, we utilized neoantigens, lipopolysaccharide and IFN-γ to induce the maturation of DCs, and then isolated DEVs derived from these mature DCs. We showed that the immune checkpoint inhibitor (anti-CTLA-4 antibody, aCTLA-4) can improve the immunostimulatory function of DEVs by directly activating T cells through immune checkpoint signal blockade. The cytokine interleukin-12 (IL-12), as one of the third signals for T cell activation, can also enhance the capability of DEVs to activate T cells directly. Based on these findings, we designed the engineered DEVs conjugated with IL-12 and aCTLA-4 (DEV@IL-12-aCTLA-4) to i

SUBMITTER: Chen J 

PROVIDER: S-EPMC12003100 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature