title: A novel liposomal recombinant lipoimmunogen enhances anti-tumor immunity.
abstract: Synthetic liposomes provide a biocompatible and biodegradable approach for delivering drugs and antigens. In addition, self-adjuvanting recombinant lipoproteins (rlipoproteins) can enhance Th1 anti-tumor immune responses via the TLR2 signaling pathway. To generate a liposomal rlipoprotein for a cancer immunotherapeutic vaccine, we assessed 3 types of synthetic liposomes for use with the rlipoproteins rlipoE7m and rlipoOVA. We determined that the cationic liposome DOTAP could stabilize anionic rlipoproteins and delay rlipoprotein release. Surprisingly, rlipoproteins and DOTAP could synergistically up-regulate CD83 expression in bone marrow-derived dendritic cells (BMDCs). Compared with other liposome formulations, the rlipoprotein/DOTAP formulation elicited higher cytotoxic T-lymphocyte (CTL) responses. To explore the mechanism of BMDC activation by rlipoprotein/DOTAP, we assessed the production of reactive oxygen species (ROS) and the TNF-α secretion of BMDCs. We observed that rlipoprotein/DOTAP induced ROS to the same extent as DOTAP did. In addition, TLR2 signaling was also required for the TNF-α secretion of rlipoprotein/DOTAP-treated BMDCs. Moreover, compared with rlipoOVA-treated BMDCs, rlipoOVA/DOTAP-treated BMDCs increased the levels of IFN-γ produced by OVA-specific T cells. We also observed that rlipoE7m/DOTAP treatment but not rlipoE7m treatment delayed tumor growth. These results indicate that the rlipoprotein/DOTAP formulation can synergistically activate BMDCs via ROS and the TLR2 signaling pathway. In summary, rlipoprotein/DOTAP is a novel and stable formulation for cancer immunotherapy.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Kuan-Yin
authors.initials: KY
authors.lastname: Shen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Li
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Chiao-Chieh
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Gunn-Guang
authors.initials: GG
authors.lastname: Liou
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Yuan-Chih
authors.initials: YC
authors.lastname: Chang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan. Electronic address: leoleng@nhri.org.tw.
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Leng
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan. Electronic address: levent@nhri.org.tw.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D008074:Lipoproteins / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D008081:Liposomes; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000485:Allergens; D019496:Cancer Vaccines; D005229:Fatty Acids, Monounsaturated; D008074:Lipoproteins; D008081:Liposomes; D050725:Papillomavirus E7 Proteins; D000644:Quaternary Ammonium Compounds; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D010047:Ovalbumin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: DOTAP; Lipoprotein; Liposome; TLR2