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

Abstract

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.

Keywords

• cancer cell membrane‐derived nanoparticles
• cancer vaccine
• tumor‐associated antigens