A New, Bio-inspired Drug Shows Potential to Combat One of America’s Leading Deadly Diseases by Boosting Immune System.

A revolutionary drug, rooted in nature, has been discovered to rejuvenate the immune cells’ ability to combat cancer.

Led by a research team at The University of Texas at Austin, the drug, when tested on mice with varying cancer types, not only stopped tumor growth but also amplified the potency of immunotherapies.

This discovery, recently highlighted in the Cancer Cell journal, holds the promise to redefine cancer treatment paradigms.

The crux of the challenge is the frequent deletion of the DNA segment named 9p21 in many cancers, a modification seen in a significant 25%-50% of cases of certain cancers.

Historically, this DNA deletion has been linked to adverse patient outcomes and a notable resistance to immunotherapies, treatments designed to amplify the body’s inherent immune defense against cancer.

This 9p21 deletion empowers cancer cells to cloak themselves from the immune system’s radar, chiefly by producing a harmful compound, MTA. This compound not only hampers immune cell function but also diminishes the impact of immunotherapies.

Everett Stone, the leading scientist behind the study, explains, “In animal models, our drug lowers MTA back down to normal, and the immune system comes back on.

“We see a lot more T cells around the tumor, and they’re in attack mode. T cells are an important immune cell type, like a SWAT team that can recognize tumor cells and pump them full of enzymes that chew up the tumor from the inside out.”

Stone projects the potential pairing of this drug with existing immunotherapies to elevate their performance.

Contributors to this transformative study include Donjeta Gjuka, formerly associated with UT and presently with Takeda Oncology, and Elio Adib, previously affiliated with the Dana-Farber Cancer Institute and now a part of Mass General Brigham.

The deletion of the 9p21 segment results in the absence of crucial genes within cancer cells. This removal encompasses genes responsible for cell cycle regulation – essential proteins that maintain a steady growth pace in healthy cells.

Without these genes, cells can proliferate without restraint, becoming cancerous. Another casualty of this deletion is a vital gene that facilitates the breakdown of the harmful compound MTA.

“Cancer gets a two-for-one when it loses both of these genes,” explains Stone. “It loses the brakes that normally keep it from growing in an uncontrolled manner. And then at the same time, it disarms the body’s police force. So, it becomes a much more aggressive and malignant kind of cancer.”

In formulating their drug proposition, Stone and the team built upon a naturally occurring enzyme that neutralizes MTA. They then incorporated adaptable polymers to it.

Stone explains, “It’s already a really good enzyme, but we needed to optimize it to last longer in the body.

“If we injected just the natural enzyme, it would be eliminated within a few hours. In mice, our modified version stays in circulation for days; in humans it will last even longer.”

With their drug, named PEG-MTAP, the research team is gearing up for more in-depth safety evaluations. They’re also on the lookout for financial support to advance it to human trials.

Source: 10.1016/j.ccell.2023.09.005

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