title: A novel emulsion-type adjuvant containing CpG oligodeoxynucleotides enhances CD8+ T-cell-mediated anti-tumor immunity.
abstract: PELC is a novel emulsion-type adjuvant that contains the bioresorbable polymer poly (ethylene glycol)-block-poly (lactide-co-ε-caprolactone) (PEG-b-PLACL), Span®85 and squalene. To investigate whether PELC is able to enhance CTL responses of antigens for treating tumor, peptides or protein antigens derived from HPV16 E7 were formulated with PELC nanoparticles and CpG oligodeoxynucleotide. We identified that PELC formulation could delay the release of antigens in vitro and in vivo. We assessed the immunogenicity of an H-2D(b)-restricted CTL epitope RAHYNIVTF (RAH) formulated with PELC or PELC/CpG and investigated the ability of these formulations to promote tumor regression. Following a single-dose subcutaneous injection in mice, we found that the RAH peptide formulated with PELC/CpG (RAH/PELC/CpG) resulted in increased numbers of IFN-γ-secreting cells and RAH-specific CD8(+) T cells and an enhanced cytotoxic T cell response compared with RAH formulated with PELC or CpG alone. The tumor-bearing mice received a single-dose injection of RAH/PELC/CpG, which induced complete tumor regression. These results demonstrated that peptide antigen formulated with PELC/CpG nanoparticles is feasible for cancer immunotherapy.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Ying-Chyi
authors.initials: YC
authors.lastname: Song
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Han-Yin
authors.initials: HY
authors.lastname: Cheng
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
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.
authors.forename: Sheng-Kuo
authors.initials: SK
authors.lastname: Chiang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan. Electronic address: huangminghsi@nhri.org.tw.
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Huang
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: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D004655:Emulsions / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006601:Hexoses / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D052162:Human papillomavirus 16 / Q000276:immunology*; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D050725:Papillomavirus E7 Proteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology; D011091:Polyesters / Q000737:chemistry / Q000627:therapeutic use; D013185:Squalene / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D004655:Emulsions; D006601:Hexoses; D009838:Oligodeoxyribonucleotides; D050725:Papillomavirus E7 Proteins; D011091:Polyesters; C059731:oncogene protein E7, Human papillomavirus type 16; C062968:lactide-caprolactone copolymer; D013185:Squalene; C005693:sorbitan trioleate
keywords: Adjuvant; Cervical cancer; CpG oligodeoxynucleotide; Human papillomavirus (HPV); Immunotherapy