P2Y 12 antibody inhibits platelet activity and protects against thrombogenesis

Given that platelet hyperactivity is known to give rise to thrombotic disorders, new and/or novel antiplatelet therapies are constantly being developed to add to, or to complement the current arsenal of agents. To this end, adenosine diphosphate (ADP) is an important platelet activator that acts by binding to the G-protein coupled P2Y and P2Y receptors. Although the contribution of the P2Y receptor to the genesis of thrombosis is well established, the parenteral arsenal of drugs targeting this receptor in clinical use is limited to cangrelor. In this study, we investigated the potential antiplatelet activity of an antibody targeting the ligand-binding domain of the P2Y receptor (abbreviated P2Y Ab). Our in vitro studies revealed that the P2Y Ab could effectively inhibit aggregation induced by ADP, as well as that triggered by the thromboxane receptor agonist U46619. Additionally, using FACS analysis, we observed reduced P-selectin, phosphatidylserine exposure and integrin activation in the presence of P2Y Ab. As for its in vivo effects, the P2Y Ab also demonstrated protection against thrombus formation; albeit this was accompanied with a bleeding diathesis (longer bleeding time). Notably, this inhibitory profile is consistent with that observed with oral anti-P2Y agents. Collectively, our findings demonstrate that the P2Y Ab functionally blocks platelet activity in vitro and in vivo, and support the notion that it can be purposed as a parenteral antiplatelet agent, to be used in conjunction with and/or as a complement to current antiplatelet therapies.