Transient antagonism of anti-CD20 monoclonal antibodies and PI3K inhibitor idelalisib in DLBCL cell lines.
Eur J Haematol
; 2018 Apr 04.
Article
em En
| MEDLINE
| ID: mdl-29617050
ABSTRACT
INTRODUCTION:
PI3K 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.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article