CD20-Specific Immunoligands Engaging NKG2D Enhance γδ T Cell-Mediated Lysis of Lymphoma Cells

Autor:	Daniela Wesch, Matthias Peipp, Andreas Humpe, J.G.J. van de Winkel, P. W. Parren, Dieter Kabelitz, Anja Muskulus, Renate Burger, Christian Kellner, Sebastian Lutz, Martin Gramatzki, Hans-Heinrich Oberg
Rok vydání:	2017
Předmět:	0301 basic medicine Receptors Antigen T-Cell gamma-delta/metabolism Cytotoxicity Immunologic Histocompatibility Antigens Class I/genetics Intercellular Signaling Peptides and Proteins/genetics Lymphoma T cell medicine.medical_treatment T-Lymphocytes Immunology GPI-Linked Proteins/genetics Biology GPI-Linked Proteins 03 medical and health sciences Interleukin 21 Cancer immunotherapy T-Lymphocytes/physiology medicine Tumor Cells Cultured Cytotoxic T cell Humans Single-Chain Antibodies/genetics ZAP70 Histocompatibility Antigens Class I NK Cell Lectin-Like Receptor Subfamily K/metabolism Receptors Antigen T-Cell gamma-delta General Medicine Natural killer T cell NKG2D Lymphoma/immunology Antigens CD20 Molecular biology Diphosphates 030104 developmental biology medicine.anatomical_structure Cell killing NK Cell Lectin-Like Receptor Subfamily K Immunotherapy/methods Intercellular Signaling Peptides and Proteins Drug Therapy Combination Immunization Immunotherapy Antigens CD20/immunology Diphosphates/therapeutic use Single-Chain Antibodies
Zdroj:	Peipp, M, Wesch, D, Oberg, H H, Lutz, S, Muskulus, A, van de Winkel, J G J, Parren, P W H I, Burger, R, Humpe, A, Kabelitz, D, Gramatzki, M & Kellner, C 2017, ' CD20-Specific Immunoligands Engaging NKG2D Enhance γδ T Cell-Mediated Lysis of Lymphoma Cells ', Scandinavian Journal of Immunology, vol. 86, no. 4, pp. 196-206 . https://doi.org/10.1111/sji.12581
ISSN:	1365-3083
DOI:	10.1111/sji.12581
Popis:	Human γδ T cells are innate-like T cells which are able to kill a broad range of tumor 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 tumor 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 tumor 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 leukemia (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 tumor-directed recombinant immunoligands which engage NKG2D may represent an attractive strategy to enhance anti-tumor cytotoxicity of γδ T cells. This article is protected by copyright. All rights reserved.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::446e5c0ed34b1f93fde1e38c1796209d https://pubmed.ncbi.nlm.nih.gov/28708284 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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