AB680, a potent and selective CD73 small molecule inhibitor, reverses the AMP/adenosine-mediated impairment of immune effector cell activation by immune checkpoint inhibitors

Abstract

Background: In the tumor microenvironment (TME), the endonucleotidase CD73 catalyzes the final step in ATP hydrolysis, generating adenosine (ADO) from adenosine monophosphate (AMP). Extracellular ADO suppresses immune function through activation of A2aR and A2bR receptors expressed on a variety of immune cells. Inhibition of CD73 eliminates a major, non-redundant, pathway of ADO production in the TME, thereby limiting immune suppression. Here we describe the ability of AB680, a small molecule CD73 inhibitor, to potentiate the activity of immune checkpoint inhibitors (ICI) in immune function assays.