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Tweaking an immune protein called interleukin-18 can overcome tumors that lure it into binding with a decoy receptor protein and render it harmless to cancer cells, new research in mice shows. In conjunction with the paper, published Wednesday in Nature, a company founded by senior author Aaron Ring announced $25 million in initial financing to create and commercialize a drug based on the discovery.

The approach adds another weapon to an immunotherapy arsenal that activates immune responses hijacked by cancer. Checkpoint inhibitors, for example, take the brakes off immune cells that should battle invaders. IL-18 is a cytokine that normally activates T cells and natural killer cells, two immune forces that fight infection, but it’s disarmed by the decoy wielded by tumors. 


Ring, who is an assistant professor of immunology at the Yale School of Medicine, thought IL-18 could be modified to avoid the decoy. The hope was that a new version of IL-18 could prevent cancer cells from taking over a normal process that dials down IL-18’s attack signals when immune cells’ work is done. Autoimmune diseases such as lupus and rheumatoid arthritis develop when the immune system is overactive, so having a way to turn off immune signals is important to health.

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