Generation of monoclonal antibodies targeting novel thrombotic interaction between neutrophils and platelets

Ischemic stroke and myocardial infarction are major cause of mortality and morbidity and aging is a major risk factor for poor outcome. Platelets and innate immune cells are key contributors to these ischemic events. Danger associated molecular pattern (DAMPs) released from innate immune cells induce platelet activation and promote a proinflammatory and procoagulant environment. In a recent unpublished study, we identified a novel anti-thrombotic pathway that can trigger non-classical clotting and is resistant to classical anti-platelet drugs. Our preliminary data shows that this triggering molecule, called S100 A8/A9, is also increased in elderly and patients with chronic inflammatory diseases and can underline similar clotting events. In this proposal, we aim to generate monoclonal antibodies targeting this receptor on platelets, called GPIb, and screening for antibodies able to block this unusual platelet activation and reduce clotting. As elderly and patients with chronic inflammatory diseases are more susceptible to ischemic event, this is a unique opportunity to develop novel antibodies targeting recently identified prothrombotic axis and support the development of a novel future anti thrombotic drug to limit ischemic cardiovascular events in elderly and during infection.