Changes in the Interaction Properties of Antibodies with Fc Receptors upon Binding to Target Antigens.

The interaction of therapeutic antibodies with Fc receptors is an important property that is actively modified to improve pharmacokinetic profiles and optimize antibody-dependent mechanisms of action. Various modifications of the Fc and hinge regions of antibodies, leading to a change in affinity with various Fc receptors, are widely covered in the literature. However, data on changes in antibody and Fc receptor interactions after antibody binding to the target antigen are poorly covered in the literature. In this work, we demonstrated a change in the affinity of the interaction of antibodies with Fc receptors after binding to the target antigen via the method of biolayer interferometry. An interesting result was a significant weakening of the interaction of FcRn and FcγRIIIa with some of the antibodies when the latter bound to the target antigen, which suggests the importance of this effect for the pharmacokinetic properties and effector mechanisms of action necessary in the treatment of oncological diseases. The sensor-based biolayer interferometry methods presented in this paper allow antibody screening to be performed to detect the effects of the reduced affinity of interactions with Fc receptors, and can be a useful tool in the early development of therapeutic antibodies.