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Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors
Joint Authors
Hassenrück, Floyd
Knödgen, Eva
Göckeritz, Elisa
Midda, Safi Hasan
Vondey, Verena
Neumann, Lars
Herter, Sylvia
Klein, Christian
Krause, Günter
Hallek, M.
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-03-19
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
The antibody-dependent cell-mediated cytotoxicity (ADCC) of the anti-CD20 monoclonal antibodies (mAbs) rituximab and obinutuzumab against the cell line Raji and isolated CLL cells and its potential impairment by kinase inhibitors (KI) was determined via lactate dehydrogenase release or calcein retention, respectively, using genetically modified NK92 cells expressing CD16-176V as effector cells.
Compared to peripheral blood mononuclear cells, recombinant effector cell lines showed substantial alloreactivity-related cytotoxicity without addition of mAbs but afforded determination of ADCC with reduced interassay variability.
The cytotoxicity owing to alloreactivity was less susceptible to interference by KI than the ADCC of anti-CD20 mAbs, which was markedly diminished by ibrutinib, but not by idelalisib.
Compared to rituximab, the ADCC of obinutuzumab against primary CLL cells showed approximately 30% higher efficacy and less interference with KI.
Irreversible BTK inhibitors at a clinically relevant concentration of 1 μM only weakly impaired the ADCC of anti-CD20 mAbs, with less influence in combinations with obinutuzumab than with rituximab and by acalabrutinib than by ibrutinib or tirabrutinib.
In summary, NK cell line-based assays permitted the sensitive detection of ADCC of therapeutic anti-CD20 mAbs against CLL cells and of the interference of KI with this important killing mechanism.
American Psychological Association (APA)
Hassenrück, Floyd& Knödgen, Eva& Göckeritz, Elisa& Midda, Safi Hasan& Vondey, Verena& Neumann, Lars…[et al.]. 2018. Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors. BioMed Research International،Vol. 2018, no. 2018, pp.1-9.
https://search.emarefa.net/detail/BIM-1124092
Modern Language Association (MLA)
Hassenrück, Floyd…[et al.]. Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors. BioMed Research International No. 2018 (2018), pp.1-9.
https://search.emarefa.net/detail/BIM-1124092
American Medical Association (AMA)
Hassenrück, Floyd& Knödgen, Eva& Göckeritz, Elisa& Midda, Safi Hasan& Vondey, Verena& Neumann, Lars…[et al.]. Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors. BioMed Research International. 2018. Vol. 2018, no. 2018, pp.1-9.
https://search.emarefa.net/detail/BIM-1124092
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1124092