Scientists are developing new vaccines that aim to prevent colon cancer in individuals with Lynch syndrome, a genetic condition that substantially elevates their risk of developing the disease and other cancers. At least three potential vaccines are in development, with two currently in early-stage clinical trials in the United States and a third beginning trials in Britain.
One such vaccine, tested by Dr. Stacy Norton, a Houston doctor whose family has been heavily affected by cancer, has shown promising results. Norton, who has Lynch syndrome, participated in a trial for a vaccine developed by MD Anderson Cancer Center. The vaccine is designed to teach the immune system to identify and intercept abnormal cells associated with Lynch syndrome before they can develop into full-fledged tumors.
Lynch syndrome is caused by inherited mutations in mismatch-repair genes, which normally help fix DNA errors that occur during cell division. When these genes are faulty, the body struggles to correct accumulated abnormalities, increasing the likelihood of tumor formation, often at younger ages. Colorectal cancer is the most common outcome, with Lynch carriers facing an 80% risk compared to the average person's 5% lifetime risk.
Individuals with Lynch syndrome also have a higher risk of other cancers, including endometrial, pancreatic, stomach, ovarian, and certain skin and brain cancers. Norton herself underwent a precautionary hysterectomy, during which early-stage cancer was discovered in her uterus.
Developing vaccines for gene-caused cancers presents a unique challenge compared to vaccines against infectious agents like viruses. "Lynch-fueled growths tend to accumulate hundreds of mutations that are going to generate proteins that are novel, not made by our normal cells," explained Dr. Eduardo Vilar-Sanchez, lead researcher on one of the potential vaccines at MD Anderson. "You can train the immune system to recognize those proteins."
A preliminary study involving 44 Lynch carriers tested a vaccine by Swiss biotech Nouscom. This vaccine aimed to help the immune system recognize specific proteins on Lynch-associated precancerous cells. Researchers reported that the vaccine stimulated tumor-eliminating T cells, and colonoscopies conducted a year later showed a reduction in precancerous growths. Dr. Norton, who participated in this study, reported being polyp-free in colonoscopies one and two years after vaccination.
Oxford University researchers are also initiating initial testing for a similar approach using mRNA technology, developed by Moderna, to target Lynch syndrome-related precancers.
Colorectal cancer diagnoses are increasing among younger adults, though the reasons remain unclear. Lynch syndrome affects approximately 1 in 279 people in the U.S., and increased awareness and genetic testing may be contributing to more diagnoses. Current U.S. guidelines recommend colorectal cancer screening to begin at age 45 for the general population, but individuals with a family history or known genetic predispositions like Lynch syndrome may require earlier or more frequent monitoring.