Many cancer treatments can be very violent on the body. Drugs can cause a lot of side effects when they attack both healthy and tumor cells.
The immune system can recognize and attack cancer cells. They only work in a small group of patients. Only a small percentage of breast cancer patients respond to one of the most common forms of immunotherapy.
What if the drugs could be used to spare the rest of the body?
My colleagues and I at the University of Chicago have designed a method to keep a promising cancer drug from beingmasked until it reaches a tumor.
The immune system responds to threats with the help of cytokines. One way they do this is by using killer T cells, a type of white blood cell that can attack cancer cells. Cancer treatments that train the immune system to kill tumors are very promising.
IL-12 is a cytokine. IL-12 is not an FDA-approved therapy for cancer patients because of its severe side effects.
IL-12 instructs immune cells to make a lot of inflammatory molecules that can damage the body.
Scientists are trying to reengineer IL-12 to be more manageable while retaining its cancer-killing effects.
One of the main differences between healthy and cancer tissue is the excess of growth-promoting enzymes.
Cancer cells overproduce certain enzymes that help them invade nearby healthy tissue and spread to other parts of the body because they are so fast growing. Cells that are healthy grow at a slower pace.
With this in mind, we masked IL-12 with a cap that covers the part of the molecule that normally binding to immune cells.
The cap is removed when it comes into contact with the tumors. When the cap is cut off, the IL-12 is activated and the killer T cells start attacking the tumor.
When we applied the masked IL-12 molecule to both healthy and tumor tissue donated by melanoma and breast cancer patients, our results confirmed that only the tumor samples were able to remove the cap.
It was shown that masked IL-12 could drive a strong immune response against tumors without causing damage to healthy organs.
We looked at how safe masked IL-12 is by measuring the damage done to the liver in mice. Immune-related side effects associated with IL-12 were absent in mice treated with masked IL-12 over a period of several weeks, indicating improved safety.
In breast cancer models, masked IL-12 resulted in a 90 percent cure rate, while treatment with a commonly used immunotherapy called a checkpoint inhibitor resulted in only a 10 percent cure rate. A 100 percent cure rate was shown in a model of colon cancer.
The modified IL-12 will be tested in cancer patients. It will take time to bring this encouraging development directly to patients, but we believe a promising new treatment is on the horizon.
Aslan Mansurov is a researcher at the University of Chicago.
This article is free to use under a Creative Commons license. The original article is worth a read.
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