Transient antagonism of anti‐ CD CD 20 monoclonal antibodies and PI PI 3K inhibitor idelalisib in DLBCL DLBCL cell lines

摘要

Abstract Introduction PI 3K 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‐ CD 20 antibody rituximab and the new type II glycoengineered anti‐ CD 20 antibody obinutuzumab in combination with the PI 3K delta inhibitor idelalisib. Methods Established DLBCL cell lines were treated with either rituximab or obinutuzumab alone or in combination with PI 3K 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 PI 3K‐signaling targets.