Despite the demonstrated effectiveness of immunoregulatory agents such as immune checkpoint blockers (ICB) on refractory cancers, these therapies work satisfactorily only in a reduced subset of patients. Further, ICB treatments are not exempt of risks and are associated to very high costs. Reliable response biomarkers are needed to identify responders and non-responders, and conventional imaging modalities and/or wet biomarkers have not proved adequate. Recently, the immune contexture of the tumor microenvironment was introduced as a new concept that classifies tumors by quantifying immune cell densities and other immune markers, and defines the chances for responding to immunotherapy. For the case of PD-1/PD-L1 inhibitors, patients are currently stratified by determining tumor expression of the target molecules from a biopsy collected prior treatment. However, the procedure is invasive, introduces risks of tumor cells dissemination and is associated with low sensitivity and specificity due to intratumoral heterogeneity. Positron emission tomography (PET) is a powerful, quantitative, non-invasive imaging technique that permits longitudinal analyses of biological processes in vivo by administration of a radiolabeled probe. In this project we aim at exploiting PET technology for doing spatial and temporal tracking of intratumoral T lymphocytes and other relevant immune-markers to stratify patients amenable for immunotherapy, and to monitor responses to therapeutic interventions.
WP1: Immuno-PET and lung cancer
Despite the demonstrated effectiveness of immunoregulatory agents such as immune checkpoint blockers (ICB) on refractory cancers, these therapies work satisfactorily only in a reduced subset of patients. Further, ICB treatments are not exempt of risks and are associated to very high costs. Reliable response biomarkers are needed to identify responders and non-responders, and conventional imaging…
WP2: Radionuclide targeted therapy and imaging in Glioblastoma
The plasticity of GB tumor cells and their ability to infiltrate adjoining brain tissue limits the effectiveness of current cancer therapies. Microglia plays an important role in GB progression. Inhibition of EGFR and CSF-1R decreases microglia-stimulated invasion of GB cells. Specific radiopharmaceuticals targeting EGFR or CSF-1R will be developed (WP3/Bergen) and applied as (i) diagnostic…
WP3: Phagocyte targeting in breast cancer
In spite of an enormous global research effort, astonishing preclinical cancer cures, and the approval of multiple formulations, nanomedicine’s impact on cancer patient care remains limited. Recently, it is becoming evident that this unsatisfactory exploitation may be tackled by considering nanodrugs’ extensive interaction with the immune system. Moreover, our collaborators recently demonstrated these interactions can…
WP4: Advancing oncological PET imaging using machine learning
The work package on machine learning will develop data analysis methods in support of the other work packages. The aim is to use expertise in artificial intelligence to help solving the medical research questions in the 180° North project. Our work focuses in particular on how to fuse the information from data acquisitions with PET,…