Williams Leenders research concentrates on the generation of novel antibodies against specific markers which discriminate tumor- from normal tissue. We have particular interest in tumor blood vessels, as antibodies with specificity against tumor vessels can be utilized to immediately cut off the blood supply to tumors. Combinations of such targeted therapies with therapies that aim at the tumor cell itself, might dramatically improve current cancer treatment modalities which initially appeared promising, but ultimately turned out disappointing.
We have available a number of orthotopic mouse models of cancer, especially melanoma and brain cancer which we use for biopanning of nanobody-phage display libraries. Nanobodies are small (15-18 kDa) recombinant antibodies, cloned from cameloids like llama, and have several properties which makes them preferable above conventional antibodies. We have isolated a number of nanobodies against tumor vessel and tumor cell markers. The ultimate aim is to apply these nanobodies for imaging (optical imaging and CT-PET) and radio-immunotherapy in preclinical models of cancer.
In another line of research we have identified a novel mechanism of metastasis which is directly related to expression of Vascular Endothelial Growth Factor-A. This relates to the escape from tumors of clusters of tumor cells, engulfed by vessel wall elements (tumor tissue) which are filtered by pulmonary vasulature and give rise to local metastatic outgrowth. The effects of neo-adjuvant VEGF-inhibition on this process, are subject of investigation, in close collaboration with the Dept of Oncology and Nuclear Medicine.
A third line of research deals with effects of angiogenesis inhibition on clinical tumors. We have extensively investigated the effects of VEGF-inhibitors in mouse models of cancer, and now these therapies are more and more applied in patients, material becomes available which allows us to investigate the effects on tumor biology in a true clinical setting.
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