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 be tuned and potentially utilized in (immuno)therapeutic settings.
At the same time, immunotherapy is rapidly developing into a powerful therapeutic modality in oncology. Nonetheless, it is now well-established that only a portion of treated patients respond and combination therapies are anticipated to greatly improve immunotherapeutic outcomes. In such synergistic therapeutic regimens, one component may serve to ‘prime’ patients for immunotherapy, for example through immune cell activation, or immune system rebalancing.
The innate immune system is emerging as an important regulator of anti-cancer adaptive immune responses; numerous mechanisms through which phagocytes and other innate immune cells can regulate anti-tumor immune responses are being discovered. Technology allowing for detection and imaging of these dynamic processes in patients will greatly benefit (immune)therapy selection and monitoring. Moreover, interference in these phagocyte specific pathways may be a potent approach to improve anti-cancer immune responses and boost immunotherapy.
In preliminary work for this project we have established that certain nanoparticles are specifically and extensively taken up by phagocytes. Now, in the “coastal collaboration”, we aim to develop these nanoparticles into diagnostic PET imaging and therapeutic agents in breast cancer. This will be facilitated by the integrative application of advanced in vivo imaging methods, including PET, MRI, and intravital microscopy, in conjunction with uniquely complementary and state-of-the-art ex vivo immune response and cell profiling methodology. Being part of the coastal collaboration offers exciting opportunities for interdisciplinary collaboration, validation of results, and free exchange of mutually beneficial tracers and protocols.