Scientists have reported that an experimental vaccine targeting one of the most common genetic drivers of pancreatic cancer, called mutant KRAS, is safe and generated a durable immune responses aimed at preventing the cancer.
KRAS mutations are present in most pancreatic cancers and most pancreatic precancerous lesions and pancreatic ductal adenocarcinoma develops from precursor lesions, such as pancreatic cysts, over many years. That means there is a vaccine window to prevent cancer from forming. This study was mKRAS-VAX, a peptide-based vaccine targeting the six most common KRAS mutations in pancreatic cancer. They recruited 20 people with a hereditary predisposition to pancreatic cancer and a pancreatic abnormality identified through imaging received the vaccine between April 2022 and February 2026. They administered four doses of the vaccine over 13 weeks. The only side effects were injection-site reactions and flu-like symptoms which required no treatment.
In 18 of the 20 participants (90 percent) they found a median 18.2X increase in mutant KRAS-specific T-cell responses. The T-cell clones remained detectable for as long as two years after vaccination. The median follow-up was about 17 months and none of the participants had a high-risk pancreatic lesion requiring surgical removal or cancer.
Mutant KRAS. Image courtesy of MD Anderson Cancer Center
This is a phase 1 clinical trial, these results dont mean it prevents pancreatic cancer, but the immune system is getting activated. If it survives phase 3 a large pharmaceutical company is going to write an even larger check to acquire technology that can prevent a real killer.
Next up is a study of high-risk patients who have had pancreatic cysts removed, so they can see the vaccine-induced immune cells in action against pre-cancerous pancreatic tissue.
Citation: S. Daniel Haldar, Amanda L. Huff, Hejia Henry. Wang, Zirui Zhu, Maureen Berg, Jiayun Lu, Nancy Sun, Elizabeth Abou Diwan, Hassan Sinan, Christopher J. Thoburn, Matthew Z. Guo, Takeichi Yoshida, Linda C. Chu, Anna K. Ferguson, Dimitrios N. Sidiropoulos, Luciane T. Kagohara, Won Jin. Ho, Katherine M. Bever, Marina Baretti, Mark Yarchoan, Daniel A. Laheru, Julie M. Nauroth, Amy M. Thomas, Hao Wang, Nilofer Saba. Azad, Michael G. Goggins, Elizabeth M. Jaffee, Neeha Zaidi; First-in-human testing of a mutant KRAS vaccine for pancreatic cancer interception in high-risk cohorts. Cancer Discov 2026; DOI: 10.1158/2159-8290.CD-25-2245
