title: Vaccination with antigen-transfected, NKT cell ligand-loaded, human cells elicits robust in situ immune responses by dendritic cells.
abstract: Both innate and adaptive immunity are crucial for cancer immunosurveillance, but precise therapeutic equations to restore immunosurveillance in patients with cancer patients have yet to be developed. In murine models, α-galactosylceramide (α-GalCer)-loaded, tumor antigen-expressing syngeneic or allogeneic cells can act as cellular adjuvants, linking the innate and adaptive immune systems. In the current study, we established human artificial adjuvant vector cells (aAVC) consisting of human HEK293 embryonic kidney cells stably transfected with the natural killer T (NKT) immune cell receptor CD1d, loaded with the CD1d ligand α-GalCer and then transfected with antigen-encoding mRNA. When administered to mice or dogs, these aAVC-activated invariant NKT (iNKT) cells elicited antigen-specific T-cell responses with no adverse events. In parallel experiments, using NOD/SCID/IL-2rγc(null)-immunodeficient (hDC-NOG) mouse model, we also showed that the human melanoma antigen, MART-1, expressed by mRNA transfected aAVCs can be cross-presented to antigen-specific T cells by human dendritic cells. Antigen-specific T-cell responses elicited and expanded by aAVCs were verified as functional in tumor immunity. Our results support the clinical development of aAVCs to harness innate and adaptive immunity for effective cancer immunotherapy.
authors.affiliation: Research Unit for Cellular Immunotherapy, The Institute of Physical and Chemical Research (RIKEN), Research Center for Allergy and Immunology (RCAI), Yokohama, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Shimizu
authors.forename: Takuya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Jun
authors.initials: J
authors.lastname: Shinga
authors.forename: Miki
authors.initials: M
authors.lastname: Asakura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kakimi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Kenichi
authors.initials: K
authors.lastname: Masuda
authors.forename: Tomoji
authors.initials: T
authors.lastname: Maeda
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sugahara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsushita
authors.forename: Keigo
authors.initials: K
authors.lastname: Nishida
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hanada
authors.forename: Jan
authors.initials: J
authors.lastname: Dorrie
authors.forename: Niels
authors.initials: N
authors.lastname: Schaft
authors.forename: Kara
authors.initials: K
authors.lastname: Bickham
authors.forename: Hisashi
authors.initials: H
authors.lastname: Koike
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ando
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Fujii
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004285:Dogs; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000637:transplantation*; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines