title: Targeting Epstein-Barr virus-transformed B lymphoblastoid cells using antibodies with T-cell receptor-like specificities.
abstract: Epstein-Barr virus (EBV) is an oncovirus associated with several human malignancies including posttransplant lymphoproliferative disease in immunosuppressed patients. We show here that anti-EBV T-cell receptor-like monoclonal antibodies (TCR-like mAbs) E1, L1, and L2 bound to their respective HLA-A*0201-restricted EBV peptides EBNA1562-570, LMP1125-133, and LMP2A426-434 with high affinities and specificities. These mAbs recognized endogenously presented targets on EBV B lymphoblastoid cell lines (BLCLs), but not peripheral blood mononuclear cells, from which they were derived. Furthermore, these mAbs displayed similar binding activities on several BLCLs, despite inherent heterogeneity between different donor samples. A single weekly administration of the naked mAbs reduced splenomegaly, liver tumor spots, and tumor burden in BLCL-engrafted immunodeficient NOD-SCID/Il2rg(-/-) mice. In particular, mice that were treated with the E1 mAb displayed a delayed weight loss and significantly prolonged survival. In vitro, these TCR-like mAbs induced early apoptosis of BLCLs, thereby enhancing their Fc-dependent phagocytic uptake by macrophages. These data provide evidence for TCR-like mAbs as potential therapeutic modalities to target EBV-associated diseases.
authors.affiliation: Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Junyun
authors.initials: J
authors.lastname: Lai
authors.affiliation: Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, National University of Singapore, Singapore;
authors.forename: Wei Jian
authors.initials: WJ
authors.lastname: Tan
authors.affiliation: Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Chien Tei
authors.initials: CT
authors.lastname: Too
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Joanna Ai Ling
authors.initials: JA
authors.lastname: Choo
authors.affiliation: Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, National University of Singapore, Singapore;
authors.forename: Lan Hiong
authors.initials: LH
authors.lastname: Wong
authors.affiliation: Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Fatimah Bte
authors.initials: FB
authors.lastname: Mustafa
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Nalini
authors.initials: N
authors.lastname: Srinivasan
authors.affiliation: Defense Medical and Environmental Research Institute, Defense Science Organization National Laboratories, Singapore; and.
authors.forename: Angeline Pei Chiew
authors.initials: AP
authors.lastname: Lim
authors.affiliation: Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Nicholas R J
authors.initials: NR
authors.lastname: Gascoigne
authors.affiliation: Defense Medical and Environmental Research Institute, Defense Science Organization National Laboratories, Singapore; and.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Hanson
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Soh Ha
authors.initials: SH
authors.lastname: Chan
authors.affiliation: Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, National University of Singapore, Singapore; Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacAry
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000821:virology; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010587:Phagocytosis / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D011948:Receptors, Antigen, T-Cell