title: Targeting CLEC9A delivers antigen to human CD141+DC for CD4+and CD8+T cell recognition.
abstract: DC-based vaccines that initiate T cell responses are well tolerated and have demonstrated efficacy for tumor immunotherapy, with the potential to be combined with other therapies. Targeting vaccine antigens (Ag) directly to the DCs in vivo is more effective than cell-based therapies in mouse models and is therefore a promising strategy to translate to humans. The human CD141+DCs are considered the most clinically relevant for initiating CD8+T cell responses critical for killing tumors or infected cells, and they specifically express the C-type lectin-like receptor CLEC9A that facilitates presentation of Ag by these DCs. We have therefore developed a human chimeric Ab that specifically targets CLEC9A on CD141+DCs in vitro and in vivo. These human chimeric Abs are highly effective at delivering Ag to DCs for recognition by both CD4+and CD8+T cells. Given the importance of these cellular responses for antitumor or antiviral immunity, and the superior specificity of anti-CLEC9A Abs for this DC subset, this approach warrants further development for vaccines.
authors.affiliation: Mater Research Institute - University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.|University of Queensland, School of Medicine, Brisbane, Queensland, Australia.|Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.|Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Kirsteen M
authors.initials: KM
authors.lastname: Tullett
authors.affiliation: Mater Research Institute - University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Leal Rojas
authors.affiliation: Mater Research Institute - University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.|University of Queensland, School of Biomedical Sciences, Brisbane, Queensland, Australia.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Minoda
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.|Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Peck S
authors.initials: PS
authors.lastname: Tan
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Corey
authors.initials: C
authors.lastname: Smith
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.|Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Irina
authors.initials: I
authors.lastname: Caminschi
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.|Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Mireille H
authors.initials: MH
authors.lastname: Lahoud
authors.affiliation: Mater Research Institute - University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.|University of Queensland, School of Biomedical Sciences, Brisbane, Queensland, Australia.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Radford
mesh_terms: D000818:Animals; D000941:Antigens; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D003713:Dendritic Cells / Q000166:cytology*; D006801:Humans; D007167:Immunotherapy; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D058990:Molecular Targeted Therapy; D011975:Receptors, Mitogen / Q000276:immunology*; D018180:Thrombomodulin
chemical_list: D000941:Antigens; D000954:Antigens, Surface; C530206:CLEC9a protein, human; D037181:Lectins, C-Type; D011975:Receptors, Mitogen; C546931:THBD protein, human; D018180:Thrombomodulin