title: Prophylactic immunization with Bubble liposomes and ultrasound-treated dendritic cells provided a four-fold decrease in the frequency of melanoma lung metastasis.
abstract: Melanoma has an early tendency to metastasize, and the majority of the resulting deaths are caused by metastatic melanoma. It is therefore important to develop effective therapies for metastasis. Dendritic cell (DC)-based cancer immunotherapy has been proposed as an effective therapeutic strategy for metastasis and recurrence due to prime tumor-specific cytotoxic T lymphocytes. In this therapy, it is important that DCs present peptides derived from tumor-associated antigens on MHC class I molecules. Previously, we developed an innovative approach capable of directly delivering exogenous antigens into the cytosol of DCs using perfluoropropane gas-entrapping liposomes (Bubble liposomes, BLs) and ultrasound. In the present study, we investigated the prevention of melanoma lung metastasis via DC-based immunotherapy. Specifically, antigens were extracted from melanoma cells and used to treat DCs by BL and ultrasound. Delivery into the DCs by this route did not require the endocytic pathway. The delivery efficiency was approximately 74.1%. DCs treated with melanoma-derived antigens were assessed for in vivo efficacy in a mouse model of lung metastasis. Prophylactic immunization with BL/ultrasound-treated DCs provided a four-fold decrease in the frequency of melanoma lung metastases. These in vitro and in vivo results demonstrate that the combination of BLs and ultrasound is a promising method for antigen delivery system into DCs.
authors.affiliation: Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oda
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Shota
authors.initials: S
authors.lastname: Otake
authors.forename: Norihito
authors.initials: N
authors.lastname: Nishiie
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Risa
authors.initials: R
authors.lastname: Koshima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nomura
authors.forename: Naoki
authors.initials: N
authors.lastname: Utoguchi
authors.forename: Nobuki
authors.initials: N
authors.lastname: Kudo
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tachibana
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D016503:Drug Delivery Systems / Q000379:methods*; D016233:Immunotherapy, Active / Q000379:methods*; D008081:Liposomes; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D058950:Melanoma-Specific Antigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014465:Ultrasonics
chemical_list: D019496:Cancer Vaccines; D008081:Liposomes; D058950:Melanoma-Specific Antigens