Cancer is a disease ranked among the most difficult to cure in the world because of its complex nature. That's why these treatments are also notoriously "barbaric" to the body itself, as it often attacks both healthy cells and tumor cells, causing a multitude of side effects.

Immunotherapies that help the immune system recognize and attack cancer cells do the same. Although there have been countless patients whose lives have been extended, in reality they only work for a small number of patients. One study found that less than 30% of breast cancer patients responded to one of the most common forms of immunotherapy.

But what if we could engineer new drugs that attack only tumor cells and avoid the healthy rest of the body?

The Promise of IL-12:

Researchers at the University of Chicago's Pritzker School of Molecular Engineering have designed a method to create such a promising cancer drug. As many of us may already know, Cytokines are proteins that can regulate how the immune system responds to threats. One way they do that is to activate "killer" T cells, a type of white blood cell that can attack cancer cells. Because cytokines can train the immune system to destroy tumours, this makes them very promising as a cancer treatment.

Current cancer treatments are inadvertently destroying healthy cells One such cytokine is interleukin-12, abbreviated IL-12. Although discovered more than 30 years ago, IL-12 is still not an FDA-approved therapy for cancer patients because of its serious side effects, such as liver damage. This is partly because IL-12 instructs immune cells to produce large amounts of inflammatory molecules that can harm the body. Now, however, researchers have been working to improve IL-12 to be more tolerable while retaining its powerful cancer-killing effects.

"Massed Assassin"

To create a safer version of IL-12, the team of researchers took advantage of one of the key differences between healthy and cancerous tissue: an excess of growth-promoting enzymes in cancer. . It is a fact that cancer cells multiply very quickly, they overproduce certain enzymes that help them invade nearby healthy tissues and metastasize to other parts of the body. Healthy cells grow at a much slower rate and produce fewer enzymes. With this data, the scientists "masked" IL-12 with a mask that covers the part of the molecule that normally binds with immune cells to activate them.

Their camouflage is only removed when it comes into contact with enzymes found in the vicinity of tumours. When these enzymes are cleaved, IL-12 is reactivated and prompts nearby killer T cells to attack the tumor. When the researchers applied these masked IL-12 molecules to both healthy and tumor tissue donated by melanoma and breast cancer patients, they found that only the New cancerous tumor can remove its disguise.

New drug based on "camouflage" is only activated to destroy tumors

This indicates that masked IL-12 is capable of promoting a robust immune response against tumors without causing damage to healthy organs. The team then went on to test the safety of the masked IL-12 by measuring biomarkers of liver damage in mice. They found that the immune-related side effects commonly associated with IL-12 were absent in the masked IL-12-treated mice over a period of several weeks, indicating a safe level of efficacy. improve.

In experimental models of breast cancer, masked IL-12 showed a cure rate of 90%, while treatment with a commonly used immunotherapy called a checkpoint inhibitor only yields a cure rate of 10%. In a colon cancer model, masked IL-12 showed a 100% cure rate.

The researchers' next step is to test the improved IL-12 in cancer patients. While it will take time to bring this encouraging development directly to patients, scientists believe a promising new treatment is on the way.

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