title: A chimeric antigen receptor for TRAIL-receptor 1 induces apoptosis in various types of tumor cells.
abstract: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its associated receptors (TRAIL-R/TR) are attractive targets for cancer therapy because TRAIL induces apoptosis in tumor cells through TR while having little cytotoxicity on normal cells. Therefore, many agonistic monoclonal antibodies (mAbs) specific for TR have been produced, and these induce apoptosis in multiple tumor cell types. However, some TR-expressing tumor cells are resistant to TR-specific mAb-induced apoptosis. In this study, we constructed a chimeric antigen receptor (CAR) of a TRAIL-receptor 1 (TR1)-specific single chain variable fragment (scFv) antibody (TR1-scFv-CAR) and expressed it on a Jurkat T cell line, the KHYG-1 NK cell line, and human peripheral blood lymphocytes (PBLs). We found that the TR1-scFv-CAR-expressing Jurkat cells killed target cells via TR1-mediated apoptosis, whereas TR1-scFv-CAR-expressing KHYG-1 cells and PBLs killed target cells not only via TR1-mediated apoptosis but also via CAR signal-induced cytolysis, resulting in cytotoxicity on a broader range if target cells than with TR1-scFv-CAR-expressing Jurkat cells. The results suggest that TR1-scFv-CAR could be a new candidate for cancer gene therapy.
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address: immkishi@med.u-toyama.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishi
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Ozawa
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamana
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; College of Basic Medical Science, Harbin Medical University, Harbin, China.
authors.forename: Aishun
authors.initials: A
authors.lastname: Jin
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Department of Surgical Oncology, Department of General Surgery and Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Zhezhu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Muraguchi
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D019169:Jurkat Cells; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000276:immunology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; D015514:Oncogene Proteins, Fusion; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human
keywords: CAR; CTL; NK cell; TRAIL