Less toxicity and better efficacy: imaging to optimise antibody-based therapies
Antibody‑based therapies are an important and rapidly growing group of medicines. These treatments are designed to recognise specific markers on cells and deliver their effect precisely where it is needed. However, many promising antibody‑based therapies still cause unwanted side effects because they can also accumulate in healthy organs and engage immune mechanisms outside the tumor. In the SILENCE project, the University Medical Center Groningen (UMCG) and the biopharmaceutical company Zymeworks are joining forces to better understand and improve the safety of these treatments. Together, they will investigate how engineered antibodies, modified in the part that interacts with the immune system (Fc region), move through the body and how their design could reduce unwanted effects.
Cancer remains one of the leading causes of death worldwide. Although antibody‑based therapies have improved outcomes for many patients, more than half of these medicines fail during development, often because of unexpected toxicity. This not only delays access to new treatments but also increases healthcare costs. Safer antibody‑based medicines could therefore make an enormous difference for patients, families, and society as a whole.
To address this challenge, SILENCE will use advanced optical and nuclear imaging to track where novel Fc‑modified antibodies travel in the body and which cells absorb them. Antibodies will be labelled with radioactivity or fluorescent dyes so that in mice their journey—from whole‑body level down to individual cells—can be followed. These parameters will then be used to build a refined model that predicts how these modified antibodies may behave in humans.
SILENCE will deliver three key results: dual-modality imaging (PET and fluorescence) to capture biodistribution from organ to cellular level; quantitative data on macrophage-mediated uptake of Fc-engineered antibodies; refinement of PBPK models with experimentally validated parameters, improving translational accuracy. Together, these outcomes will accelerate the development of next‑generation treatments with fewer side effects, also beyond oncology.
