Human IgG1 antibodies suppress angiogenesis in a target-independent manner

Researchers have shown monoclonal antibodies, precision drugs used for many diseases, have unexpected, untargeted effects on blood vessels. These drugs are the most widely used therapy for conditions driven by aberrant angiogenesis – the abnormal growth of blood vessels – such as certain cancers and blinding disorders. A large international research team, led by Jayakrishna Ambati at the University of Kentucky, now reports a novel unexpected mechanism by which monoclonal antibodies can block blood vessel growth regardless of their molecular target. They showed that this generic anti-angiogenic effect involves signaling through a cell-surface receptor known as FcγRI. These findings raise concerns about possible unwanted “off-target” effects of antibody drugs, but also identify FcγRI as a possible target for new drugs to control angiogenesis,