(1100-A) The impact of ruxolitinib and tocilizumab on IL-6 evoked phospho-STAT3 induction across immune cell subsets

Abstract: Designing suitable biomarker assays to evaluate target engagement of therapeutic agents supports hypothesis testing in clinical trials. As an example, we have used phospho flow cytometry to investigate the phosphorylation of STAT3 in response to the inflammatory cytokine IL-6 across various human immune cell subsets including CD4 and CD8 T cells, NK and NK-T cells, Tregs, B cells and monocytes. IL-6 differentially induced phospho-STAT3 across immune subsets.

We have used this assay to compare two therapeutic agents targeting the IL-6 pathway, tocilizumab and ruxolitinib. Tocilizumab blocks IL-6 signaling at the IL-6 receptor whereas ruxolitinib inhibits IL-6-evoked STAT3 phosphorylation through inhibition of JAK1/2. We compare and contrast the sensitivity of immune cell subsets to these two inhibitors by measuring the induction of STAT3 phosphorylation by ‘low’ and ‘high’ dose IL-6.

On-going studies are utilising this approach to investigate the nature of IL-6 signaling in health and disease.