Understanding how immune cell function is impacted by novel therapies in patients with B cell malignancies

Summary In recent years, new non-chemotherapy based small molecule inhibitors such as Venetoclax and Ibrutinib have been shown to offer improved outcomes in patients with B cell malignancies. Our existing data has demonstrated that these therapies have a significant impact on patient immune function when used long term which will be explored further in this project.

Project Details

Patients with B cell malignancies, such as Chronic Lymphocytic Leukaemia (CLL) and Mantle Cell Lymphoma (MCL) have traditionally been treated with chemotherapy, which does not often result in a cure, and has significant side effects.  Novel treatments specifically targeting cell death pathways in B cells, such as Venetoclax and Ibrutinib, have offered improved outcomes in many patients. However, few studies have investigated the impact of these diseases on immune function or the impact of novel therapies on the immune system particularly in patients on long term therapy. We are particularly interested in identifying prognostic immune biomarkers that might help predicting clinical outcomes, studying the function of specific immune cell subsets and determining whether long term control of B cell malignancy might lead to immunological recovery.

The ACRF Translational Research Laboratory at the RMH has collated a unique biobank from patients with a range of B cell malignancies, collected prior to treatment, and on treatment with novel therapies. This biobank contains multiple blood samples from patients on longitudinal treatments (up to 5 years on clinical trials), providing the possibility to track immune function over time. Our laboratory also has expertise in many immune function assays, such as multi-parameter flow cytometery to profile immune cell subsets, T cell function assays, and cytokine detection. Furthermore, we have extensive experience in gene profiling, including Nanostring, and cutting-edge Digital Spatial Profiling technology in tissues.

The project(s) on offer in 2020 in the ACRF laboratory will allow students to profile the immune system of patients with B cell malignancies, on unique clinical trials, using our biobank of prospectively collected samples.  Human ethics approval has already been acquired. Current studies underway in the ACRF laboratory have identified a number of exciting projects for a dedicated student with a desire to understand how novel therapies impact long-term outcomes in haematology cancer patients.  A background in immunology, molecular biology or cellular biology is preferable.