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
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
New technique overcomes technological barrier in 3D brain imaging
Scientists at the Swiss Light Source SLS have succeeded in mapping a piece of brain tissue in 3D at unprecedented resolution using X-rays, non-destructively. The breakthrough overcomes a long-standing technological barrier that had limited [...]
Scientists Uncover Hidden Blood Pattern in Long COVID
Researchers found persistent microclot and NET structures in Long COVID blood that may explain long-lasting symptoms. Researchers examining Long COVID have identified a structural connection between circulating microclots and neutrophil extracellular traps (NETs). The [...]
This Cellular Trick Helps Cancer Spread, but Could Also Stop It
Groups of normal cbiells can sense far into their surroundings, helping explain cancer cell migration. Understanding this ability could lead to new ways to limit tumor spread. The tale of the princess and the [...]
New mRNA therapy targets drug-resistant pneumonia
Bacteria that multiply on surfaces are a major headache in health care when they gain a foothold on, for example, implants or in catheters. Researchers at Chalmers University of Technology in Sweden have found [...]
Current Heart Health Guidelines Are Failing To Catch a Deadly Genetic Killer
New research reveals that standard screening misses most people with a common inherited cholesterol disorder. A Mayo Clinic study reports that current genetic screening guidelines overlook most people who have familial hypercholesterolemia, an inherited disorder that [...]
Scientists Identify the Evolutionary “Purpose” of Consciousness
Summary: Researchers at Ruhr University Bochum explore why consciousness evolved and why different species developed it in distinct ways. By comparing humans with birds, they show that complex awareness may arise through different neural architectures yet [...]
Novel mRNA therapy curbs antibiotic-resistant infections in preclinical lung models
Researchers at the Icahn School of Medicine at Mount Sinai and collaborators have reported early success with a novel mRNA-based therapy designed to combat antibiotic-resistant bacteria. The findings, published in Nature Biotechnology, show that in [...]
New skin-permeable polymer delivers insulin without needles
A breakthrough zwitterionic polymer slips through the skin’s toughest barriers, carrying insulin deep into tissue and normalizing blood sugar, offering patients a painless alternative to daily injections. A recent study published in the journal Nature examines [...]
