The human natural killer cytotoxic cell line NK-92, once armed with a murine CD16 receptor,represents a convenient cellular tool for the screening of mouse mAbs according to their ADCC potential |
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Authors: | Béatrice Clémenceau Régine Vivien Catherine Pellat Michael Foss Gilles Thibault Henri Vié |
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Institution: | 1.INSERM U892; Nantes, France;2.Centre Hospitalier Universitaire de Nantes; Nantes, France;3.CNRS UMR 7292, Université François Rabelais de Tours and Centre Hospitalier Universitaire de Tours, Laboratoire d’Immunologie; Tours, France |
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Abstract: | To take advantage of the large number of well-characterized mouse immunoglobulins (IgGs) for the study of antibody-dependent cell-mediated cytotoxicity (ADCC) in human cells, we armed human cytotoxic lymphocytes with a mouse receptor for the Fc portion of IgG antibodies. The human ΝΚ−92 natural killer cell line was transduced with a mouse receptor gene (mCD16), which was stably expressed on the cell surface (referred to as NK-92mCD16). When tested against a B-lymphoblastoid cell line (BLCL) coated with mouse anti-CD20 IgG1, IgG2a or IgG2b monoclonal antibodies (mAbs), the newly expressed mouse Fc receptor enabled the NK-92mCD16 cells to kill the BLCL by ADCC. Next, using the NK-92mCD16 we compared mouse mAbs directed at B lineage specific CD antigens for their ability to induce ADCC against human Epstein-Barr virus- infected B lymphoblastoid (for anti-CD19, -CD20 and -CD21) or against myeloma (for anti-CD38 and –CD138) target cells. Our results demonstrated that the “NK-92mCD16 assay” allows convenient and sensitive discrimination of mouse mAbs for their ability to mediate ADCC in a human cellular system. In addition, our results provide examples of dissociation between opsonization and target cell killing through ADCC. These “murinized” human effector cells thus represent a convenient cellular tool for the study of ADCC. |
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Keywords: | ADCC transfection mouse CD16 human lymphocyte NK xenogenic |
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