Tu130 - Humanized in Vivo Models Supporting the Identification of Novel Inhibitory Receptor Agonists for the Treatment of Immune-mediated Diseases

stephanie grebinoski; stephen lutz; Mike Cianci; Andre stanlie; rebecca goydel; Ishan Sharma; Jyothsna visweswaraiah; nathan. higginson-scott; kevin otipoby; daniela cipolletta

Abstract Text: Evidence in both animal models and patients demonstrate that inhibitory receptors (IRs) play an important role in limiting autoimmunity. Similarly, blockade of checkpoint inhibitory receptors has been proven to be efficacious for the treatment of cancer and often associated with new onset of immune-related adverse events. Since the loss or blocking of inhibitory receptor pathways can result in inflammation, we hypothesized that agonism of these pathways should restore normal immune homeostasis. However, the generation of agonistic antibodies is often challenged by the lack of inhibitory receptor mouse orthologue cross-reactivity thus limiting our options to evaluate putative therapeutic agonists pre-clinically. Here we will survey the promise and limitations of using humanized animal models to interrogate efficacy and mechanism of action of novel inhibitory receptor agonists for the treatment of immune-mediated diseases.