학술논문
CD20-Specific Immunoligands Engaging NKG2D Enhance γδ T Cell-Mediated Lysis of Lymphoma Cells.
Document Type
Academic Journal
Author
Peipp M; Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.; Wesch D; Institute of Immunology, Christian-Albrechts-University of Kiel, Kiel, Germany.; Oberg HH; Institute of Immunology, Christian-Albrechts-University of Kiel, Kiel, Germany.; Lutz S; Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.; Muskulus A; Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.; van de Winkel JGJ; Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.; Genmab, Utrecht, The Netherlands.; Parren PWHI; Genmab, Utrecht, The Netherlands.; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.; Burger R; Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.; Humpe A; Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.; Kabelitz D; Institute of Immunology, Christian-Albrechts-University of Kiel, Kiel, Germany.; Gramatzki M; Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.; Kellner C; Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
Source
Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0323767 Publication Model: Print Cited Medium: Internet ISSN: 1365-3083 (Electronic) Linking ISSN: 03009475 NLM ISO Abbreviation: Scand J Immunol Subsets: MEDLINE
Subject
Language
English
Abstract
Human γδ T cells are innate-like T cells which are able to kill a broad range of tumour cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumour cell killing. The two immunoligands, designated MICA:7D8 and ULBP2:7D8, respectively, enhanced cytotoxicity of ex vivo-expanded γδ T cells against CD20-positive lymphoma cells. Both Vδ1 and Vδ2 γδ T cells were triggered by MICA:7D8 or ULBP2:7D8. Killing of CD20-negative tumour cells was not induced by the immunoligands, indicating their antigen specificity. MICA:7D8 and ULBP2:7D8 acted in a dose-dependent manner and induced cytotoxicity at nanomolar concentrations. Importantly, chronic lymphocytic leukaemia (CLL) cells isolated from patients were sensitized by the two immunoligands for γδ T cell cytotoxicity. In a combination approach, the immunoligands were combined with bromohydrin pyrophosphate (BrHPP), an agonist for Vδ2 γδ T cells, which further enhanced the efficacy in target cell killing. Thus, employing tumour-directed recombinant immunoligands which engage NKG2D may represent an attractive strategy to enhance antitumour cytotoxicity of γδ T cells.
(© 2017 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Foundation for the Scandinavian Journal of Immunology.)
(© 2017 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Foundation for the Scandinavian Journal of Immunology.)