Targeting Epstein-Barr virus-transformed B lymphoblastoid cells using antibodies with T-cell receptor-like specificities.

Autor:	Lai J; Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine., Tan WJ; 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;, Too CT; Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine., Choo JA; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine., Wong LH; Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, National University of Singapore, Singapore;, Mustafa FB; Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine., Srinivasan N; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine., Lim AP; Defense Medical and Environmental Research Institute, Defense Science Organization National Laboratories, Singapore; and., Zhong Y; Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine., Gascoigne NR; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine., Hanson BJ; Defense Medical and Environmental Research Institute, Defense Science Organization National Laboratories, Singapore; and., Chan SH; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine., Chen J; 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., MacAry PA; Immunology Programme, Life Sciences Institute, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2016 Sep 08; Vol. 128 (10), pp. 1396-407. Date of Electronic Publication: 2016 Jun 23.
DOI:	10.1182/blood-2016-03-707836
Abstrakt:	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. (© 2016 by The American Society of Hematology.)
Databáze:	MEDLINE
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