Résumé
OBJECTIVES : Monoclonal antibodies (mAbs) are an important part of targeted therapies in cancerology particularly by reaching their targets overexpressed on tumor cells. However, most of these targets are also expressed at basal level by healthy tissues generating some toxicities (“on target - off tumor”). Affinity antibody properties for their targets is a key component of this targeting efficiency [1]–[4]. The aim of this project is to study the role of antibody affinity/avidity in the possible reduction of the “on target - off tumor” phenomenon. METHODS : We developed a range of human antibodies by phage display processing on human EGFR target with different affinity levels checked by enzyme-linked immunosorbent assay (ELISA). We concluded this in vitro validation by cytometry assays on cells lines characterized by a gradient of density EGF receptors level (from 103 to 106 receptors per cells). RESULTS : In vitro, using ELISA, we ranked 6 antibodies produced as full IgG format as low, medium and high affinity against EGFR compare with the high affinity positive control Cetuximab. Cytometry experiments on the different cells lines showed that only medium affinity level antibodies could bind overexpressed EGFR present on cancer cells lines but not on cancer cells lines with medium and low expression EGFR level which mimic healthy tissues. CONCLUSION : We seems to be able to target overexpressed EGFR cell lines but spare healthy tissues with medium affinity level antibody. Next, our hypothesis will be confirmed in vivo. Antibodies will be radiolabelled with Zirconium-89 to perform non-invasive biodistribution studies with Positron Emission Tomography [5]–[7].