Cytokines are proteins that can modulate how the immune system responds to threats. One way they do this is by activating killer T cells, a type of white blood cells that can attack cancer cells. Because cytokines can train the immune system to kill tumors, this makes them very promising as cancer treatments.
One such cytokine is interleukin-12, or IL-12. Though it was discovered more than 30 years ago, IL-12 still isn’t an FDA-approved therapy for cancer patients because of its severe side effects, such as liver damage. This is in part because IL-12 instructs immune cells to produce a large amount of inflammatory molecules that can damage the body.
Scientists have since been working to reengineer IL-12 to be more tolerable while retaining its powerful cancer-killing effects.
Masking the killer
To create a safer version of IL-12, my colleagues and I took advantage of one of the main differences between healthy and cancerous tissue: an excess of growth-promoting enzymes in cancers. Because cancer cells proliferate very rapidly, they overproduce certain enzymes that help them invade the nearby healthy tissue and metastasize to other parts of the body. Healthy cells grow at a much slower pace and produce fewer of these enzymes.
With this in mind, we “masked” IL-12 with a cap that covers the part of the molecule that normally binds to immune cells to activate them. The cap is removed only when it comes into contact with enzymes found in the vicinity of tumors. When these enzymes chop off the cap, IL-12 is reactivated and spurs nearby killer T cells to attack the tumor.