ESR 8: State-of-the-art in vivo PET-CT imaging of immune cell subsets in chronic inflammatory diseases and cancer

PhD research

Host:

Dr. S.W. Tas

Internist-Rheumatologist

Department of Rheumatology & Clinical Immunology

Laboratory for Experimental Immunology

Amsterdam UMC, location AMC

Meibergdreef 9

Duration: 48 months

Background

Patients with chronic inflammatory diseases, such as rheumatoid arthritis (RA), and cancer are increasingly treated with immunotherapy. In chronic inflammatory diseases these are mainly the so-called biologics (including anti-TNF, anti-CD20 therapy or CTLA4-Ig), while cancer patients are treated with anti-angiogenesis therapy (including anti-VEGF) and checkpoint blockers (including anti-PD- L1 and anti-CTLA4). However, not all patients respond well to initiated treatment and this is most likely dependent on the extent to which the mechanism that is being targeted plays a role in the disease process in the individual patient. Collecting information on the microenvironment such as the extent to which soluble mediators (i.e. growth factors , chemokines and cytokines) and/or certain immune cells (for example T cell infiltration into a tumor or synovial tissue pathotype) are involved in the disease process by means of the minimally invasive method PET-CT using specific tracers before initiation of treatment, may allow us to predict whether a patient will respond well to the selected therapy. On the basis of this, certain treatments could possibly also be combined to achieve greater effectiveness.

Using this approach we expect to prevent that patients are being treated (for a long period of time) with ineffective therapies. Moreover, this may contribute to controlling health care costs, both locally and at the macroeconomic level.

Aim: to set up novel imaging techniques to visualize immune cells and soluble mediators in chronic inflammatory diseases and cancer.

Approach 

Testing of several readily available tracers in vitro and testing in animal models of arthritis and cancer; correlation with histology; possibly assess toxicity

Development of novel human tracers

Pilot dose-finding studies in the first patients (rheumatoid arthritis and cancer).

Additional human studies including analysis of synovial tissue biopsies and tumor tissues (liver metastases); correlation of imaging data with histology

Data analysis and planning of a large RCT

The department of Rheumatology and Clinical Immunology has a well-functioning bioplatform in which arthroscopic or ultrasound-guided synovium and lymph node biopsies are collected. This is already highly integrated into healthcare. The oncology department has a leading role in GIOCA in which diagnostics and treatment are coordinated in a superior way. Amsterdam UMC has extensive expertise in the implementation of PET imaging in clinical care for patients. In addition, there is a GMP facility for the production of PET tracers so that safe use in patients is guaranteed. Finally, all knowledge is available to quantify PET signals for monitoring disease activity and response to therapy. Implementation of the imaging strategies proposed in this project in healthcare is therefore expected to proceed smoothly.

Expected results

The proposed research will provide novel tools to non-invasively obtain information on the contribution of certain immune cells and/or soluble mediators to the disease process. Ultimately, we expect that this information can be used to guide treatment decisions.

Our research team

The Amsterdam Rheumatology & immunology Center, AMC/University of Amsterdam (Head: Prof.R.F. van Vollenhoven) is recognized as a NFU Center of Expertise for vasculitis and has extensive experience with fundamental and translational immunological research. The proposed project will be supervised by Dr. S.W. Tas, an expert in signal transduction and immunology. He received a NWO Veni grant in 2008, followed by a ZonMw Clinical Fellowship in 2011. These grants enabled him to develop a novel research line “The role of signalling pathways in chronic inflammation” and to build an (independent) research group. Besides working as a rheumatologist, he heads the AMC bioplatform and currently supervises 6 PhD-students, a postdoc and a technician. Dr. Tas is also member of the steering group of the ARCH vasculitis consortium that aims to improve care for patients with vasculitis. Dr. J.P. van Hamburg is a senior-postdoc in the group of Dr. Tas who obtained expertise on immunology, including the analysis of T-B-cell interaction, and molecular biology at the Erasmus MC (Rotterdam) and the University of California (San Diego, USA). The current project will be done in close collaboration with the group of Prof. C.D. Pusey (Imperial College School of Medicine, London, UK) who has extensive experience in a versatile animal model of ANCA-associated vasculitis. The proposed research will be performed primarily in the Laboratory for Experimental Immunology of the AMC (Head: Prof. T. Geijtenbeek).