‘Masked’ cancer drug secretly trains immune system to kill tumors while sparing healthy tissue, reducing treatment side effects

Many cancer therapies are well-known for being brutal to the human body. The medications frequently target both healthy and malignant cells, resulting in a slew of undesirable side effects. Immunotherapies, which assist the immune system in identifying and attacking cancer cells, are no exception. They only function in a subset of patients, despite the fact that they have helped numerous people live longer lives. Only around 30% of breast cancer patients react to one of the most frequent types of immunotherapy, according to one research.

But what if medications could be designed to target only tumor cells while leaving the rest of the body unharmed? To that goal, my colleagues and I at the Pritzker School of Molecular Engineering at the University of Chicago invented a mechanism that causes chaos by "masking" a potential cancer medication until it reaches a tumor.

Immunotherapy aids the immune system in identifying and destroying cancer cells.

IL-12. promise of

Cytokines are proteins that regulate the immune system's response to threats. Activating killer T cells, a kind of white blood cell that may assault cancer cells, is one technique to do this. Cytokines are particularly promising as cancer therapies because they can teach the immune system to fight tumors.

Interleukin-12 (IL-12) is one such cytokine. IL-12, while being discovered more than 30 years ago, is still not an FDA-approved cancer treatment due to major side effects such as liver damage. This is partially due to the fact that IL-12 stimulates immune cells to create high amounts of inflammatory chemicals that are potentially harmful to the body.

Since then, scientists have been attempting to make IL-12 more bearable while keeping its cancer-killing properties.

Mask the killer

My colleagues and I used one of the primary distinctions between healthy and malignant tissue to generate a safer version of IL-12: the amount of enzymes that drive growth in cancer. Because cancer cells multiply so quickly, they overproduce enzymes that help them infiltrate healthy tissue and spread to other regions of the body. Healthy cells have a modest growth rate and generate fewer enzymes.

In light of this, we "masked" IL-12 by covering the portion of the molecule that typically binds to activate immune cells with a cap. When the cap comes into touch with enzymes located surrounding the tumor, it is removed. When these enzymes remove the cap, IL-12 is reactivated, causing killer T cells in the area to attack the tumor.

Our findings indicated that only tumor samples were able to remove the cap when these disguised IL-12 molecules were given to both healthy and tumor tissue provided by patients with melanoma and breast cancer. This suggested that disguised IL-12 might trigger a powerful immune response against tumors while causing no damage to healthy organs.

We next measured liver damage indicators in mice to see if IL-12 is safe. We discovered that mice treated with masked IL-12 for several weeks had less immunological adverse effects than mice treated with unmasked IL-12, indicating greater protection.

Our masked IL-12 resulted in a 90 percent cure rate in the breast cancer model, but treatment with checkpoint inhibitors, a typical immunotherapy, resulted with just a 10% cure rate. Masked IL-12 had a cure rate of 100 percent in a colon cancer model.

The next step will be to put modified IL-12 to the test in cancer patients. While bringing this exciting research directly to patients will take time, we believe a promising new therapy is on the horizon.