Engineering nanostructured pure cancer cell membrane-derived vesicles as a novel therapeutic cancer vaccine

Abstract

Extracted cancer cell membrane carries the antigens of the parent tumor cell. This autologous antigen repertoire presents cancer cell membrane-derived nanoparticles highly immunogenic to the body's immune system. Cancer cell membrane-derived nanoparticles antigenically recapitulate the parental cancer cells and can be exploited to induce immune response reactive with tumor-associated antigens (TAAs). The use of the cancer cell membrane-derived nanoparticles to deliver immunostimulatory adjuvants facilitates the cross-presentation of tumor antigens by antigen-presenting cells and their costimulation, triggering potent antigen-specific T responses to eliminate established tumors. These nanoparticles can be engineered to carry immunostimulatory signals to facilitate the cross-presentation of TAAs and the induction of potent antitumor immunity. In this study, cancer cell membrane-based vesicles (CCMVs) are prepared from B16 melanoma cells and engineered to deliver the immunological agent polyinosinic:polycytidylic acid (poly-IC). We show that CCMV is preferentially uptaken by bone marrow-derived dendritic cells (BMDCs) as compared to other cell types (macrophages, fibroblasts). The efficient delivery of poly-IC to BMDCs results in enhanced antigen cross-presenting capability of BMDCs and T-cell activation. Additionally, immunization of mice with poly-IC-carrying CCMV elicits a potent antitumor immune response. In conclusion, poly-IC-decorated tumor-derived CCMV may be used as a therapeutic vaccine to potentiate antitumor immunity.