title: Antitumor activity of human γδ T cells transducted with CD8 and with T-cell receptors of tumor-specific cytotoxic T lymphocytes.
abstract: The difficulty in the induction and preparation of a large number of autologous tumor-specific cytotoxic T lymphocytes (CTL) from individual patients is one of major problems in their application to adoptive immunotherapy. The present study tried to establish the useful antitumor effectors by using γδ T cells through tumor-specific TCRαβ genes transduction, and evaluated the efficacy of their adoptive transfer in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice model. The TCRαβ gene was cloned from the HLA-B15-restricted CTL clone specific of the Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1). The cloned TCRαβ as well as the CD8 gene were transduced into γδ T cells induced from peripheral blood lymphocytes (PBL). Cytotoxic T lymphocyte activity was examined using a standard 4 h (51) Cr release assay. Mice with a xenotransplanted tumor were treated with an injection of effector cells. Successful transduction of TCRαβ was confirmed by the staining of KK-LC-1-specific tetramers. The γδ T cells transduced with TCRαβ and CD8 showed CTL activity against the KK-LC-1-positive lung cancer cell line in a HLA B15-restricted manner. Adoptive transfer of the effector cells in a mice model resulted in marked growth suppression of KK-LC-1- and HLA-B15-positive xenotransplanted tumors. Co-transducing TCRαβ and CD8 into γδ T cells yielded the same antigen-specific activity as an original CTL in vitro and in vivo. The TCRαβ gene transduction into γδ T cells is a promising strategy for developing new adoptive immunotherapy.
authors.affiliation: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. hanagiri@med.uoeh-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hanagiri
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shigematsu
authors.forename: Koji
authors.initials: K
authors.lastname: Kuroda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Baba
authors.forename: Hironobu
authors.initials: H
authors.lastname: Shiota
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ichiki
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Nagata
authors.forename: Manabu
authors.initials: M
authors.lastname: Yasuda
authors.forename: Tomoko
authors.initials: T
authors.lastname: So
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takenoyama
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta