title: A purified recombinant lipopeptide as adjuvant for cancer immunotherapy.
abstract: Synthetic lipopeptides have been widely used as vaccine adjuvants to enhance immune responses. The present study demonstrated that the tryptic N-terminal fragment of the lipoprotein rlipo-D1E3 (lipo-Nter) induces superior antitumor effects compared to a synthetic lipopeptide. The lipo-Nter was purified and formulated with protein or peptide vaccines to determine if lipo-Nter could be used as a novel adjuvant and could induce antitumor immunity in a cervical cancer model. Purified lipo-Nter activated the maturation of bone marrow-derived dendritic cells (BM-DCs), leading to the secretion of TNF-α through TLR2/6 but not TLR1/2. A recombinant mutant HPV16 E7 (rE7m) protein was mixed with lipo-Nter to immunize the mice; the anti-E7 antibody titers were increased, and the T helper cells were skewed toward the Th1 fate (increased IL-2 and decreased IL-5 secretion). Single-dose injection of rE7m and lipo-Nter inhibited tumor growth, but the injection of rE7m alone did not. Accordingly, lipo-Nter also enhanced the antitumor immunity of the E7-derived peptide but not the synthetic lipopeptide (Pam3CSK4). We demonstrated that the lipo-Nter of a bacterial-derived recombinant lipoprotein is a novel adjuvant that could be used for the development of a new generation of vaccines.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Ying-Chyi
authors.initials: YC
authors.lastname: Song
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Hsueh-Hung
authors.initials: HH
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: I-Hua
authors.initials: IH
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan ; Graduate Institute of Immunology, China Medical University, Taichung 40447, Taiwan.
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan ; Graduate Institute of Immunology, China Medical University, Taichung 40447, Taiwan.
authors.forename: Pele
authors.identifier: 0000-0003-4197-7160
authors.initials: P
authors.lastname: Chong
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan ; Graduate Institute of Immunology, China Medical University, Taichung 40447, Taiwan.
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Leng
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan ; Graduate Institute of Immunology, China Medical University, Taichung 40447, Taiwan.
authors.forename: Shih-Jen
authors.identifier: 0000-0002-8736-1452
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D055666:Lipopeptides / Q000276:immunology* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology* / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000628:therapy; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D015848:Interleukin-5; D055666:Lipopeptides; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D022223:Vaccines, Subunit; C059731:oncogene protein E7, Human papillomavirus type 16
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