title: Transfer of mRNA Encoding Invariant NKT Cell Receptors Imparts Glycolipid Specific Responses to T Cells and γδT Cells.
abstract: Cell-based therapies using genetically engineered lymphocytes expressing antigen-specific T cell receptors (TCRs) hold promise for the treatment of several types of cancers. Almost all studies using this modality have focused on transfer of TCR from CD8 cytotoxic T lymphocytes (CTLs). The transfer of TCR from innate lymphocytes to other lymphocytes has not been studied. In the current study, innate and adaptive lymphocytes were transfected with the human NKT cell-derived TCRα and β chain mRNA (the Vα24 and Vβ11 TCR chains). When primary T cells transfected with NKT cell-derived TCR were subsequently stimulated with the NKT ligand, α-galactosylceramide (α-GalCer), they secreted IFN-γ in a ligand-specific manner. Furthermore when γδT cells were transfected with NKT cell-derived TCR mRNA, they demonstrated enhanced proliferation, IFN-γ production and antitumor effects after α-GalCer stimulation as compared to parental γδT cells. Importantly, NKT cell TCR-transfected γδT cells responded to both NKT cell and γδT cell ligands, rendering them bi-potential innate lymphocytes. Because NKT cell receptors are unique and universal invariant receptors in humans, the TCR chains do not yield mispaired receptors with endogenous TCR α and β chains after the transfection. The transfection of NKT cell TCR has the potential to be a new approach to tumor immunotherapy in patients with various types of cancer.
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shinga
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kawamura
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dörrie
authors.affiliation: Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Schaft
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Iyoda
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Fujii
mesh_terms: D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000235:genetics; D006017:Glycolipids / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008024:Ligands; D055611:Natural Killer T-Cells / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D014162:Transfection
chemical_list: D006017:Glycolipids; D008024:Ligands; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004247:DNA