Cancer Drug Kills Cancer Cells

Although interleukin-12 caused adverse side effects, researchers have long hypothesized that it 

would be a potent cancer treatment. A new form of the molecule has been created by Pritzker 

Molecular Engineering researchers that does not activate until it enters a tumor, 

where it kills cancer cells.

Numerous cancer treatments are notoriously harsh on the body; they assault healthy cells simultaneously with tumor cells and result in a wide range of side effects. 

The Pritzker School of Molecular Engineering (PME) at the University of Chicago has now developed a strategy to prevent one potential cancer drug from causing such damage. Interleukin-12 has been modified by scientists into a new, “masked” form that is only activated when it comes into contact with a tumor. 

The study on the molecule, also known as IL-12, was published in the journal Nature Biomedical Engineering.

“Our research shows that this masked version of IL-12 is much safer for the body, but it possesses the same anti-tumor efficacy as the original,” said Aslan Mansurov, a postdoctoral research fellow and first author of the new paper. 

He carried out the IL-12 engineering work with Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering, who co-leads PME’s Immunoengineering research theme with professor Melody Swartz.

Researchers have discovered that IL-12 strongly activates lymphocytes, which are immune cells with the ability to kill tumor cells. Early IL-12 clinical studies, however, were stopped in the 1990s due to the patients’ harsh, toxic side effects. 

The same immune activation that set off a series of events that killed the cancer cells also caused significant inflammation throughout the body. The study of IL-12 was discontinued, at least in its natural form.


However, Mansurov, Hubbell, Swartz, and others came up with a plan to revive the potential of IL-12. What if the medication could pass through the body without triggering the immune system? T

They created a “masked” molecule with a cap covering the region of IL-12 that typically binds immune cells. Only tumor-associated proteases, a collection of molecular scissors located close to tumors to aid them in destroying the good tissue around them, can cut off the cap. 

The IL-12 becomes active and is then able to activate an immune response against the tumor when the proteases remove the cap.  READ MORE...

Good Gut Bacteria

Researchers of synthetic biology based at the Massachusetts Institute of Technology (MIT) in the US have devised a system to protect the gut microbiome from the effects of antibiotics.

The new study, published in Nature Biomedical Engineering, reports on the successful use in mice of a “live biotherapeutic” – a genetically engineered bacterium that produces an enzyme which breaks down antibiotics in the gut.

“This work shows that synthetic biology can be harnessed to create a new class of engineered therapeutics for reducing the adverse effects of antibiotics,” says MIT professor James Collins, the paper’s senior author.
The dark side of antibiotics

Antibiotics – substances that kill or inhibit the growth of bacteria – are hugely important in fighting bacterial infections.

But there’s a dark side to antibiotics too. Increasing human use of antibiotics has contributed to the rise of antibiotic resistance, which has made many bacterial diseases increasingly difficult to successfully treat.

Antibiotic treatment can also kill off bacteria in our resident healthy gut microbiome – the trillions of microbes that live in our gastrointestinal tract and assist with food digestion, immune development and vitamin synthesis.

This causes two problems: firstly, we can lose the benefits provided by our good bacteria; and secondly, this disruption can tip the balance of the microbial ecosystem towards species that cause harm.

In some cases, these indiscriminate effects of antibiotics can have life-threatening consequences. In the US, about 15,000 deaths each year are attributed to diarrhoea and colitis (inflammation of the colon) caused by overgrowth of the bacterium Clostridium difficile following antibiotic overuse.

So, while antibiotics are an important and necessary tool to fight bacterial infections, working to limit antibiotic resistance and damage to the gut microbiome are key priorities for research.  READ MORE...