Transient antagonism of anti-CD20 monoclonal antibodies and PI3K inhibitor idelalisib in DLBCL cell lines

Zöllner, Anna-Katharina; Peter, Nico; Zimmermann, Yvonne; Hutter, Grit; Hiddemann, Wolfgang und Dreyling, Martin (2018): Transient antagonism of anti-CD20 monoclonal antibodies and PI3K inhibitor idelalisib in DLBCL cell lines. In: European Journal of Haematology, Bd. 101, Nr. 2: S. 143-149

Abstract

IntroductionPI3K inhibitors are evaluated for relapsed and refractory Diffuse large B-cell lymphoma (DLBCL) patients. Objective: As rituximab has shown to influence B-cell receptor (BCR) signaling, we investigated the interaction of anti-CD20 antibody rituximab and the new type II glycoengineered anti-CD20 antibody obinutuzumab in combination with the PI3K delta inhibitor idelalisib. Methods: Established DLBCL cell lines were treated with either rituximab or obinutuzumab alone or in combination with PI3K delta inhibitor idelalisib. Results: Rituximab and to a lesser extent obinutuzumab monotherapy resulted in a temporary upregulation of p-Akt, p42/44, and p38 signaling pathways. Idelalisib reduced p-Akt expression. Rituximab antagonized the p-Akt downregulation at early time points, while obinutuzumab did not interfere with idelalisib's effects. In cell growth analysis, early antagonism could also be detected. Conclusion: The combination of idelalisib with CD antibodies shows an initial antagonism of rituximab but not obinutuzumab in downregulation of PI3K-signaling targets.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0902-4441
• Sprache: Englisch