Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p><jats:styled-content style="fixed-case">PI</jats:styled-content>3K inhibitors are evaluated for relapsed and refractory Diffuse large B‐cell lymphoma (<jats:styled-content style="fixed-case">DLBCL</jats:styled-content>) patients.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>As rituximab has shown to influence B‐cell receptor (<jats:styled-content style="fixed-case">BCR</jats:styled-content>) signaling, we investigated the interaction of anti‐<jats:styled-content style="fixed-case">CD</jats:styled-content>20 antibody rituximab and the new type <jats:styled-content style="fixed-case">II</jats:styled-content> glycoengineered anti‐<jats:styled-content style="fixed-case">CD</jats:styled-content>20 antibody obinutuzumab in combination with the <jats:styled-content style="fixed-case">PI</jats:styled-content>3K delta inhibitor idelalisib.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Established <jats:styled-content style="fixed-case">DLBCL</jats:styled-content> cell lines were treated with either rituximab or obinutuzumab alone or in combination with <jats:styled-content style="fixed-case">PI</jats:styled-content>3K delta inhibitor idelalisib.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Rituximab and to a lesser extent obinutuzumab monotherapy resulted in a temporary upregulation of p‐Akt, p42/44, and p38 signaling pathways.</jats:p><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The combination of idelalisib with <jats:styled-content style="fixed-case">CD</jats:styled-content> antibodies shows an initial antagonism of rituximab but not obinutuzumab in downregulation of <jats:styled-content style="fixed-case">PI</jats:styled-content>3K‐signaling targets.</jats:p></jats:sec>