When 20 people at high genetic risk for pancreatic cancer received an experimental vaccine, not a single one developed the disease during the study period. That's the striking finding from a Phase I clinical trial of a new vaccine called mKRAS-VAX, published in the journal Cancer Discovery.
Pancreatic cancer is one of the most deadly cancers. It often goes undetected until it's already spread, and the five-year survival rate remains low. About 10% of cases run in families due to inherited genetic changes passed from parent to child. These high-risk individuals are usually monitored with regular imaging scans — but many early warning signs are too small to see.
"Successful interception that could reduce the occurrence of pancreatic cancer would be a major achievement," said Dr. Michael Goggins, one of the researchers, quoted in the study.
The new vaccine works by training the immune system to recognize and attack cells carrying mutant versions of a gene called KRAS. These faulty KRAS genes are present in more than 90% of pancreatic cancers and their early precancerous lesions. The mKRAS-VAX vaccine targets six of the most common KRAS mutations found in pancreatic disease.
The trial participants — 20 people with genetic risk factors and suspicious pancreatic cysts — received the vaccine through injections under the skin. They got three priming doses over five weeks, followed by a booster dose at week 13. Researchers then tracked their immune responses over time.
The results exceeded expectations. The vaccine sparked strong, mutant-KRAS-specific immune responses in 90% of participants, and those responses lasted up to two years after vaccination. "This long-lasting response is particularly noteworthy when assessing for possible interception of cancer, which requires long-lasting immunity," said Dr. Sandra Zaidi.
After a median follow-up of 16.5 months, none of the vaccinated individuals developed pancreatic cancer. As an extra sign of promise, researchers looked at participants' pancreatic cysts — tiny fluid-filled sacs that can sometimes become cancerous. Among vaccinated people, 37.5% showed cyst reduction or complete disappearance. That compares to just 6.8% in a similar unvaccinated group.
"Overall, this study represents the first proof of concept for the use of vaccines for interception of pancreatic cancer in human patients," Zaidi said.
The researchers caution this is early-stage work. Larger studies are needed to confirm the findings and determine the best timing and approach for vaccination. Still, the team sees this as a turning point in cancer prevention for people facing high genetic risk.
"This research underscores the need for further funding to support the development of strategies that can intercept and prevent cancer development in high-risk individuals," said Dr. Elizabeth Jaffee, another co-author.