Synthetic immune protein rallies the troops to fight cancer

Immunotherapy is a promising potential treatment for cancer, but it still has kinks to iron out. In a new study from Yale, researchers have identified a “jamming signal” that cancer uses to hide from the immune system – and importantly, engineered a synthetic immune cell that can fight back.

The natural version of this immune cell is called interleukin-18 (IL-18), and it’s just one weapon of many that the immune system deploys. Specifically, IL-18 is known to rally T cells and to fight off infections, as well as diseases like cancer.

So the researchers set out to investigate what these countermeasures might be – and they found one. Usually, IL-18 activates immune cells by binding to a receptor on their surface. But the team found that many types of cancer express a high amount of a protein called interleukin-18 binding protein (IL-18BP). As the name suggests, this also binds to IL-18, preventing it from activating the other immune cells. In that way, IL-18BP acts like a kind of decoy receptor.

With that mechanism in mind, the team then examined how they might be able to bypass it. They used a process called directed evolution, which mimics natural selection to guide proteins towards desired traits – in this case, those that ignore the decoy and only bind to the real receptor. After searching through around 300 million variations of IL-18, the researchers eventually found just what they were looking for.