HOUSTON — MD Anderson researchers reported that a vaccine developed by Swiss biotech Nouscom increased tumor-eliminating T cells and reduced precancerous growths in participants with Lynch syndrome. The findings from the phase 1b/2 trial were published in Nature Medicine.

The study, titled Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial, detailed results from a group of 45 individuals. Dr. Eduardo Vilar-Sanchez of the MD Anderson Cancer Center served as the lead researcher for the trial.

Dr. Stacy Norton, an obstetrician/gynecologist at Houston Methodist Willowbrook Hospital, was one of the participants. For the first time since 2014, her colonoscopies one and two years after vaccination were polyp-free. The broader group showed fewer precancerous growths and no advanced polyps one year after receiving the vaccine.

The Nouscom vaccine is designed to teach the immune system to identify 209 specific abnormalities found in precancers caused by Lynch syndrome. "Lynch-fueled growths tend to accumulate hundreds of mutations that are going to generate proteins that are novel, not made by our normal cells," Vilar-Sanchez said. He added that medical professionals can use this biological distinction to target the disease. "You can train the immune system to recognize those proteins," he said.

Norton, 59, has a personal history with the condition that drives her interest in preventive measures. She was 7 years old when her mother died of colon cancer, and her sister died of a brain tumor at age 25. A gene test in her 40s confirmed she had Lynch syndrome, leading her to undergo a precautionary hysterectomy where surgeons discovered early-stage cancer.

"It gives me hope," Norton said. She noted the potential impact on the screening burden for others with the genetic mutation. "Perhaps they won’t have to have a colonoscopy every single year for the rest of their lives," she said.

Lynch syndrome is caused by an inherited genetic mutation in mismatch-repair genes, which normally help fix DNA mistakes that occur when cells multiply. When these genes are faulty, the body struggles to stop a buildup of abnormalities that can lead to tumors. Colorectal cancer is the most common consequence, though carriers also face higher risks for endometrial, pancreatic, stomach, ovarian, certain skin cancers, and a kind of brain tumor.

An estimated 1 million Americans have Lynch syndrome, affecting about 1 in 279 people. While the average person has a 5% risk of developing colorectal cancer during their lifetime, a carrier’s risk can reach as high as 80% depending on the faulty gene inherited. Tumors associated with the syndrome often develop before age 50.

About 158,000 people are diagnosed with colorectal cancer in the U.S. each year, with most diagnoses occurring in people over 50. However, cases in younger adults are increasing. Current U.S. guidelines call for routine colorectal cancer screening to begin at age 45 for the average person, while those with Lynch syndrome are often urged to get yearly colonoscopies to spot and remove precancerous polyps.

At least three potential Lynch syndrome vaccines are currently in development. Two of these vaccines are in early clinical trials in the U.S. while a third is beginning trials in Britain. Oxford University researchers are beginning initial testing of a vaccine made by Moderna using mRNA technology. Moderna is based in Massachusetts.

Scientists are also awaiting results from a study comparing ImmunityBio’s Tri-Ad5 vaccine to a placebo. ImmunityBio is based in California. Previous research has explored other preventive avenues, including a 2020 study in Gut titled Naproxen chemoprevention promotes immune activation in Lynch syndrome colorectal mucosa. A 2023 study in Molecular Aspects of Medicine reviewed advances in vaccine development for the condition.

Dr. John Marshall, an oncologist at Georgetown University and an adviser to the Colorectal Cancer Alliance, was not involved with the Nouscom vaccine study. "Can we even further stimulate the immune system to keep up with Lynch syndrome-spurred tumor formation?" Marshall asked.

Vilar-Sanchez expects a larger study of the Nouscom vaccine to begin early next year. More data on a booster shot given to a subset of the current study participants is expected this fall.

Why It Matters

With colorectal cancer risk reaching 80% for Lynch syndrome carriers, current prevention relies on frequent colonoscopies to remove polyps. The Nouscom vaccine trial results suggest a potential shift toward immune-based prevention that could reduce this screening burden for the estimated 1 million Americans with the condition. This development occurs as at least two other vaccines enter early clinical trials, signaling a broader move to target the genetic mutations driving tumor growth before cancer develops.