title: CpG-ODN-stimulated dendritic cells act as a potent adjuvant for E7 protein delivery to induce antigen-specific antitumour immunity in a HPV 16 E7-associated animal tumour model.
abstract: We previously reported that both E7 and CpG-oligodeoxynucleotide (ODN) are required for protecting animals from human papillomavirus (HPV) 16 E7-associated tumour challenge. Here we investigate dendritic cells (DC)-based approach in this protection. In the study, we isolated bone marrow-derived DC and stimulated DC with E7 and ODN. In vitro stimulation of DC with E7 plus ODN resulted in more production of interleukin-12, as compared to that with E7 or ODN alone. Further injection with E7+ODN-stimulated DC resulted in more significant tumour protection, as compared to stimulation with E7 or ODN alone. We further evaluated the levels of immune responses induced by DC stimulated with E7+ODN. We observed little enhancement of E7-specific antibody and T helper cell proliferative responses by E7+ODN stimulation, as compared to E7 stimulation. However, there was some enhancement of interferon-gamma (IFN-gamma) production from CD4+ T cells and a more significant production of IFN-gamma from CD8+ T cells by E7+ODN stimulation, as compared to E7 stimulation alone. This was consistent with intracellular IFN-gamma staining levels of CD8+ T cells. Tumour protection further appeared to be mediated by CD8+ T cells, as determined by in vivo T-cell depletion. Thus, these data suggest that upon ODN stimulation DC might function as a potent adjuvant for E7 protein delivery for induction of protective cellular immunity against HPV E7-associated tumour challenge.
authors.affiliation: Department of Microbiology, The Catholic University of Korea, Seoul, Korea.
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Eun Ha
authors.initials: EH
authors.lastname: Won
authors.forename: Su Mi
authors.initials: SM
authors.lastname: Bae
authors.forename: Woong-Shick
authors.initials: WS
authors.lastname: Ahn
authors.forename: Jae-Bok
authors.initials: JB
authors.lastname: Park
authors.forename: Jeong-Im
authors.initials: JI
authors.lastname: Sin
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D018664:Interleukin-12; D007371:Interferon-gamma