Exploring Time-Resolved Characterization of the Heterogeneity and Dynamics of Ligand-Receptor Interactions on Living Cells
Pages 94-104
Pavel Barta, Karl Andersson, Frantisek Trejtnar and Jos Buijs

DOI: http://dx.doi.org/10.6000/1927-7229.2014.03.02.4
Published: 30 April 2014

Abstract: The time-resolved interaction analysis was applied on living cells to extract detailed interaction characteristics of two therapeutic antibodies and natural ligand binding to the same receptor expressed on two different human carcinoma cell lines.

The observed differences in the antibody binding characteristics and heterogeneity could be attributed both to differences in antibodies and cell lines. The stability of antibody binding to EGFR on cells is significantly higher than the binding stability to isolated EGFR. This higher stability can be of fundamental importance as it potentially shifts the drug-target residence time into a domain that is limiting in pharmacokinetics and hence is of importance for in vivo drug efficacy.

EGF binding to its receptor was more heterogeneous and it was demonstrated for the first time that time-resolved interaction measurements in combination with Interaction Map analysis could be used to probe the dynamics of a ligand (protein) induced dimerization and/or oligomerization process.

Keywords: Cetuximab, EGF receptor, Interaction Map, kinetics, panitumumab, tracer.