Emma completed her PhD at the Brighton and Sussex Medical School, where she obtained experience using a range of laboratory techniques including flow cytometry, cell migration analysis, and western blotting. Additionally, Emma has qualifications in Biology (BSc, University of Sussex) and Molecular Medicine and Cancer (MSc, University of Sheffield) and has experience working as both a Medical Laboratory Assistant and Clinical Trials Administrator for the NHS. In her current position, she is working on ‘Overcoming Ibrutinib and Venetoclax resistance in Chronic Lymphocytic Leukaemia’, with funding from the Medical Research Council.
Ibrutinib is a BTK inhibitor, approved for the frontline treatment of Chronic Lymphocytic Leukaemia. Whilst ibrutinib has proven very effective at releasing tissue resident CLL cells from protective lymph node/bone marrow niches and inhibiting further migration to these areas, some CLL cells appear to evade these restrictions. Toll-like receptor 9 (TLR9) is an innate pattern recognition receptor and we have previously shown CLL cell migration to increase following stimulation with the TLR9 agonist ODN 2006. This left figure shows that both ibrutinib and the TLR9 antagonist ODN INH-18 to reduce CLL cell migration in ODN 2006-stimulated CLL cells (n=6), and that a combination of both ibrutinib and ODN INH-18 reduces migration significantly further. In the right figure the Combination Index (CI) analysis shows ibrutinib and ODN INH-18 to be synergistic in all 6 patient samples (i.e., CI<1). At the half maximal effective dose (ED50), the mean CI was 0.2, indicating a strong synergistic effect. TLR9 is therefore a potential candidate for a dual targeted approach to the treatment of CLL (Kennedy et al., BLOOD, 2021).