Intercepting danger
For people born with Lynch syndrome, cancer risk isn’t hypothetical. The inherited condition, found in about 1 in 280 people, sharply increases the odds of developing colorectal, endometrial and several other cancers, often at younger ages.
Researchers at the University of Texas MD Anderson Cancer Center are exploring a less invasive option. Their Nature Medicine study last week describes how an experimental vaccine called NOUS-209 awakened the immune systems of 45 Lynch syndrome carriers, training their defenses to find and eliminate abnormal cells early.
“Current management strategies for Lynch syndrome patients — frequent screenings or elective preventive surgery — are life-changing interventions that help prevent cancer development but can significantly affect quality of life,” said Eduardo Vilar-Sanchez, who led the research. “By teaching the immune system to recognize and attack abnormal cells, this therapy offers a promising new approach.”
When we met, he said people with Lynch syndrome face repeated medical surveillance. The hope, he said to me, is to shift the focus from fear of cancer toward a sense of control over it.
Everyone in the trial mounted a strong immune response. Blood samples showed activated immune cells that recognized and killed cancer-related targets in the lab. Those responses strengthened after booster doses and showed signs of memory, the holy grail of vaccination.
More striking was what doctors saw on follow-up colonoscopies. A year after treatment, participants had fewer precancerous lesions, and none developed advanced polyps — “a reassuring hint of potential clinical activity,” Vilar-Sanchez said — that the immune system was doing surveillance work normally left to scopes and surgeons.
The vaccine was well tolerated, with no serious side effects. The findings suggest that the immune system can be coached to keep a lookout for the cellular slip-ups that spark cancer — a kind of biological early warning.
The idea builds on a quirk of Lynch syndrome biology. Because patients carry defects in DNA repair, their abnormal cells accumulate distinctive errors that act like neon signs to the immune system once it’s been shown what to look for.
The vaccine addresses a glaring gap in care. Screening saves lives but dominates them, and preventive surgery can mean removing healthy organs to avoid future disease. An immune-based option wouldn’t replace those tools anytime soon, though it might change how aggressively they’re used.
Vilar-Sanchez said his group is now planning a larger, multi-year study to test how durable the immune responses are. “Hopefully this is going to re-energize the field and thinking on vaccine development for cancer prevention, which will be very, very cool,” he said.
For families who live expecting cancer as a rite of passage, even the possibility of immune interception changes the conversation. — Jason Gale