Antibodies in Drug Discovery Agenda

Antibodies are essential tools both in fundamental and therapeutic-oriented research to determine the localization, analyze the expression and study the function of various antigens (e.g. proteins, lipids, post-translational modifications) in cells and in tissues. In addition, in the recent years, a large proportion of therapeutic success came from the identification and functionalization of highly specific antibodies. Hence, it is essential to get a fast access to highly specific and functional antibodies. While animal immunization,  followed by monoclonal selection, antibody cloning and humanization, is still the standard approach, in vitro selection is an attractive alterative as it reduces the time needed to get the binders, cuts down the cost and above all provide excellent controls of the conditions of selection. We constructed a highly diverse library based on a synthetic humanized single domain scaffold displayed on M13 phages. Full in vitro selection were carried out using purified antigens or tumor cells. High affinity antibodies, including conformation-specific antibodies, were obtained. Single domain binders were then used as intrabody or as targeting antibodies.