Many cancer treatments are notoriously savage on the body. Drugs often attack both healthy cells and tumor cells, causing a plethora of side effects. Immunotherapies that help the immune system recognize and attack cancer cells are no different. Though they have prolonged the lives of countless patients, they work in only a subset of patients. One study found that fewer than 30% of breast cancer patients respond to one of the most common forms of immunotherapy.
But what if drugs could be engineered to attack only tumor cells and spare the rest of the body? To that end, my colleagues and I at the University of Chicago’s Pritzker School of Molecular Engineering have designed a method to keep one promising cancer drug from wreaking havoc by “masking” it until it reaches a tumor.
The promise of IL-12
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.
When we applied these masked IL-12 molecules 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. This indicated that masked IL-12 could potentially drive a strong immune response against tumors without causing damage to healthy organs.
We then examined how safe masked IL-12 is by measuring liver damage biomarkers in mice. We found that immune-related side effects typically associated with IL-12 were notably absent in mice treated with masked IL-12 over a period of several weeks, indicating improved safety.
In breast cancer models, our masked IL-12 resulted in a 90% cure rate, while treatment with a commonly used immunotherapy called a checkpoint inhibitor resulted in only a 10% cure rate. In a model of colon cancer, masked IL-12 showed a 100% cure rate.
Our next step is to test the modified IL-12 in cancer patients. While it will take time to bring this encouraging development directly to patients, we believe a promising new treatment is on the horizon.

News
A potential milestone in cancer therapy
Researchers from the University of Bern, Inselspital, University Hospital Bern, and the University of Connecticut have made a significant breakthrough in the fight against cancer. They identified a previously unknown weak point of prostate [...]
Cardiovascular Crystal Ball: New Tool Predicts Future Heart Disease Risk
Faculty members at the UM School of Medicine have created a cutting-edge tool that enables the early identification and assessment of risks in vulnerable patients. Heart disease, being the leading cause of death globally, [...]
Scientists analyze a single atom with X-rays for the first time
In the most powerful X-ray facilities in the world, scientists can analyze samples so small they contain only 10,000 atoms. Smaller sizes have proved exceedingly difficult to achieve, but a multi-institutional team has scaled [...]
AI Demonstrates Superior Performance in Predicting Breast Cancer
AI algorithms outperformed traditional clinical risk models in a large-scale study, predicting five-year breast cancer risk more accurately. These models use mammograms as the single data source, offering potential advantages in individualizing patient care [...]
Stanford Medicine Reveals: Tiny DNA Circles Defying Genetic Laws Drive Cancer Formation
Tiny circles of DNA harbor cancer-associated oncogenes and immunomodulatory genes promoting cancer development. They arise during the transformation from pre-cancer to cancer, say Stanford Medicine-led team. Tiny circles of DNA that defy the accepted laws of [...]
Death to Blood Cancer Cells: New Drug Combination Could Revive the Power of Leading Treatment
Future clinical trials will be conducted to investigate whether the combination of chloroquine and venetoclax can prevent disease recurrence. Although new drugs have been developed to induce cancer cell death in individuals with acute [...]
Illuminating Science: X-Rays Visualize How One of Nature’s Strongest Bonds Breaks
Scientists have deciphered how an activated catalyst breaks down the strong carbon-hydrogen bonds in potent greenhouse gas methane, according to a study published in Science. Using advanced X-ray technology and quantum-chemical calculations, they tracked the [...]
Using magnetic nanoparticles as a rapid test for sepsis
Qun Ren, an Empa researcher, and her team are currently developing a diagnostic procedure that can rapidly detect life-threatening blood poisoning caused by staphylococcus bacteria. Staphylococcal sepsis is fatal in up to 40% of [...]
Team develops nanoparticles to deliver brain cancer treatment
University of Queensland researchers have developed a nanoparticle to take a chemotherapy drug into fast growing, aggressive brain tumors. Research team lead Dr. Taskeen Janjua from UQ's School of Pharmacy said the new silica [...]
Tumor Avatars – A New Approach to Personalized Cancer Treatment
A team from the University of Geneva (UNIGE) has devised a novel method for customizing treatments by testing them on artificial tumors. Determining the optimal treatment for colon cancer can be challenging as each [...]
STING Like a Bee: MIT’s Revolutionary Approach to Cancer Immunotherapy
A cancer vaccine combining checkpoint blockade therapy and a STING-activating drug eliminates tumors and prevents recurrence in mice. MIT researchers have engineered a therapeutic cancer vaccine that targets the STING pathway, vital for immune response [...]
AI Battles Superbugs: Helps Find New Antibiotic Drug To Combat Drug-Resistant Infections
The machine-learning algorithm identified a compound that kills Acinetobacter baumannii, a bacterium that lurks in many hospital settings. Using an artificial intelligence algorithm, researchers at MIT and McMaster University have identified a new antibiotic that can kill a [...]
Cancer and AI – Can ChatGPT Be Trusted?
A study published in the Journal of The National Cancer Institute Cancer Spectrum delved into the increasing use of chatbots and artificial intelligence (AI) in providing cancer-related information. The researchers discovered that these digital resources accurately [...]
Breathing New Life: Oxygen Therapy Improves Heart Function in Long COVID Patients
A small trial has found that hyperbaric oxygen therapy (HBOT) may help restore proper heart function in patients with post-COVID syndrome, with participants in the HBOT group experiencing a significant increase in global longitudinal [...]
Wireless Brain-Spine Interface: A Leap Towards Reversing Paralysis
Summary: In a pioneering study, researchers designed a wireless brain-spine interface enabling a paralyzed man to walk naturally again. The ‘digital bridge’ comprises two electronic implants — one on the brain and another on the [...]
New study reveals a gel that promises to wipe out brain cancer for good
An anti-cancer gel promises to wipe out glioblastoma permanently, a feat that's never been accomplished by any drug or surgery. So what makes this gel so special? Scientists at Johns Hopkins University (JHU) have [...]