title: Modifying Antigen-Encapsulating Liposomes with KALA Facilitates MHC Class I Antigen Presentation and Enhances Anti-tumor Effects.
abstract: For a successful anti-cancer vaccine, antigen presentation on the major histocompatibility complex (MHC) class I is a requirement. To accomplish this, an antigen must be delivered to the cytoplasm by overcoming the endosome/lysosome. We previously reported that a lipid nanoparticle modified with a KALA peptide (WEAKLAKALAKALAKHLAKALAKALKA), an α-helical cationic peptide, permits the encapsulated pDNA to be efficiently delivered to the cytoplasm in bone marrow-derived dendritic cells (BMDCs). Herein, we report on the use of KALA-modified liposomes as an antigen carrier, in an attempt to induce potent antigen-specific cellular immunity. The subcutaneous injection of KALA-modified ovalbumin (OVA)-encapsulating liposomes (KALA-OVA-LPs) elicited a much more potent OVA-specific cytotoxic T lymphocyte activity and anti-tumor effect in comparison with particles that were modified with octa-arginine (R8), a cell-penetrating peptide (R8-OVA-LPs). In addition, the numbers of OVA-specific CD8+T cells were increased by immunization the KALA-OVA-LPs. The treatment of BMDCs with KALA-OVA-LPs induced a substantial MHC class I antigen presentation. Furthermore, the acidic pH-dependent membrane destabilization activity of KALA-OVA-LPs strongly suggests that they are able to escape from endosomes/lysosomes and thereby deliver their cargos to the cytoplasm. Collectively, the KALA-modified liposome is a potential antigen delivery platform for use as a protein vaccine.
authors.affiliation: Department of Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo City, Hokkaido 060-0812, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Miura
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 263-8675, Japan. Electronic address: akitahide@chiba-u.jp.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 263-8675, Japan.
authors.forename: Naho
authors.initials: N
authors.lastname: Tateshita
authors.affiliation: Department of Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo City, Hokkaido 060-0812, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo City, Hokkaido 060-0812, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D007114:Immunization; D008081:Liposomes; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000941:Antigens; D019496:Cancer Vaccines; D016207:Cytokines; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C105114:KALA amphipathic peptide; D008081:Liposomes; D010455:Peptides; D010047:Ovalbumin
keywords: KALA peptides; MHC class I presentation; anti-cancer vaccines; dendritic cells; liposomes; protein vaccines