Identification and characterization of selective FcγRIIb binders and their potential of IMPACTing immune-mediated diseases

Abstract Biologics targeting multiple pathways and/or cell types simultaneously have the potential to restore normal immune homeostasis. Inhibitory checkpoint receptor agonism by antibodies benefits from higher order clustering for strong activation, which can be achieved antibody Fc binding gamma receptors (FcγRs). However, many of current agonist non discriminately bind activating FcγRs. This has trigger inflammatory cytokines antigen presenting cells (APCs) or cause dependent cellular cytotoxicity (ADCC). Clustering inhibitory receptor, FcγRIIb provide superior avoiding cytokine responses and limiting APC activation. is 93% homologous FcγRIIa, designing molecules that specifically presents a challenge our IMPACT platform address. Using integrated machine learning, structural biology traditional campaigns, we identified selective molecules, characterized their IMPACTing immune-mediated diseases.