Non-selective antagonists acting at a stable cell-cell interface have the potential to induce signaling

A model, based on receptor occupancy theory, for signaling due to receptor A and co-receptor B colocalization in the presence of a stable cell-cell interface reveals that a non-selective antagonist of receptor A with affinity for a receptor C on the trans-cell can induce as well as inhibit the signal due to A. As a result, assertion of selectivity for agents acting in such a system should be supported by measurement of signal when the co-receptor B is absent. For conditions where the co-receptor B is non-functional, the model reveals the potential to rescue function through bifunctional ligands, such as bispecific antibodies, antibody conjugates or even bifunctional tethered small molecules.