Figure 3.
Panel A: Biparatopic antibodies targeting two distinct epitopes on the same receptor (for example LAG3) to enhance receptor engagement and signaling through avidity. Panel B: Bispecific antibodies engaging different receptors (such as PD1 and TCR/CD3 or LAG3) on the same cell to induce receptor clustering at the immune synapse. Panel C: IgG subclass differences (IgG1, Ig G2, IgG3), hinge flexibility, and post-translational modifications impacting antibody structure and function. Panel D: Fc gamma receptor interactions where Fc gamma RII binding can stabilize antibody interactions at the immune synapse for agonism, while limiting binding to activating receptors such as Fc gamma RIII helps prevent cell depletion through antibody-dependent cellular cytotoxicity (ADCC).
Approaches to target IRs or disease/tissue. (A) Biparatopic antibodies targeting both orthosteric and allosteric sites can enhance binding via avidity. (B) bsAbs can be cis targeting to engage molecules on the same cells to induce receptor clustering at the immune synapse (IS). (C) IgG subclass, hinge flexibility, and posttranslational modifications can impact antibody function. (D) FcγRII binding may stabilize antibody at the IS for agonism, and engineering of antibodies to prevent binding to other FcR can prevent depletion of cells through ADCC. The figure was created with BioRender.