Single Domain Antibodies: From Conformational Sensors to Bispecific Antibodies for Immunotherapy

Single domain antibodies (AKA nanobodies), the variable domains of some camelid antibodies, have interesting properties, including high production yields and stability but also the ability to bind unusual epitopes such as cleft and cavities. We are using them as innovative tools such as biosensors able to capture the conformation states of some membrane receptors such as EGFR or metabotropic glutamate receptors (mGluRs) on living cells. Combined with time-resolved FRET assays, they can reveal the fine mechanisms of receptor activation at the cell surface.Single domain antibodies also represent efficient building blocks to create bispecific molecules that we are using to immunomolulate effectors cells in the tumor microenvironment. An example will be given with the activation of effector cells such as NK cells in the context of tumor cells expressing low amount of tumor antigens, outperforming the classical ADCC mechanisms.