Hassenrueck, Floyd, Knoedgen, Eva, Goeckeritz, Elisa, Midda, Safi Hasan ORCID: 0000-0002-2822-6293, Vondey, Verena, Neumann, Lars, Herter, Sylvia, Klein, Christian ORCID: 0000-0001-7594-7280, Hallek, Michael and Krause, Guenter (2018). Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors. Biomed Res. Int., 2018. LONDON: HINDAWI LTD. ISSN 2314-6141

Full text not available from this repository.

Abstract

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 mu M 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hassenrueck, FloydUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knoedgen, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goeckeritz, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Midda, Safi HasanUNSPECIFIEDorcid.org/0000-0002-2822-6293UNSPECIFIED
Vondey, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumann, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herter, SylviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, ChristianUNSPECIFIEDorcid.org/0000-0001-7594-7280UNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krause, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-200102
DOI: 10.1155/2018/1023490
Journal or Publication Title: Biomed Res. Int.
Volume: 2018
Date: 2018
Publisher: HINDAWI LTD
Place of Publication: LONDON
ISSN: 2314-6141
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC LYMPHOCYTIC-LEUKEMIA; IN-VITRO; THERAPEUTIC ANTIBODIES; MONOCLONAL-ANTIBODIES; PRECLINICAL ACTIVITY; KINASE INHIBITORS; RITUXIMAB; EFFICACY; GA101; IBRUTINIBMultiple languages
Biotechnology & Applied Microbiology; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/20010

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item