Bone Marrow Dendritic Cells Derived Microvesicles for Combinational Immunochemotherapy against Tumor

Abstract

AbstractVarious types of cell can change the cytoskeleton and shed microvesicles (MVs) with biomimic properties as parent cells in response to stimuli. To take use of the drug package capability of MVs and the potent antigen presentation property of dendritic cells (DCs), DC‐derived antigenic MVs are constructed by priming DCs with tumor‐derived MVs and then encapsulating a chemotherapeutic drug during MVs shedding. This kind of MVs exhibit significant inhibition on melanoma tumor growth and metastasis. The MV‐encapsulated chemotherapeutics can induce direct cytotoxicity and immunogenic cell death in tumor cells. Moreover, a robust antitumor immunity is induced in both, the tumor‐draining lymph node and the tumor microenvironment as the infiltration and activation of T lymphocytes increases. This kind of MVs is further explored in a hepatic ascites model with remarkable prolonged overall survival of mice. More importantly, the MVs can extend the survival of 60% mice more than 150 d without ascites even after rechallenging the tumor twice. This study demonstrates that antigenic MVs with chemotherapeutics possess great potential in cancer immunochemotherapy.