Cell-targeted PD-1 agonists are potent NK cell inhibitors

We have generated a novel targeted bispecific PD-1 molecule, to achieve tissue-specific immune suppression for the treatment of immune-mediated inflammatory diseases. These targeted PD-1 agonists have shown potent T cell inhibition and here we describe an additional effect on NK cell activation. We show that PD-1 pathway activation modifies NK cell gene expression and decreases their inflammatory and cytotoxic functions. Targeted PD-1 agonist molecules, inhibiting T cells and NK cells in a tissue-specific manner offer a new promising treatment for autoimmune and inflammatory diseases.