Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, with most cases diagnosed at advanced stages and relatively few options for early detection.
New clinical trial results published in Cancer Discovery suggest an investigational vaccine targeting common KRAS mutations may offer a strategy to intercept the disease before cancer develops in individuals at elevated risk.
The off-the-shelf synthetic long peptide vaccine, known as mKRAS-VAX, was designed to target the six most common KRAS mutations found in PDAC and many pancreatic precancerous lesions. Mutations in the KRAS gene are the primary oncogenic drivers in more than 90% of pancreatic ductal adenocarcinomas.
Early evidence supports a cancer interception strategy
Researchers enrolled 20 individuals considered at high risk for PDAC because of hereditary cancer predisposition and radiographic evidence of pancreatic lesions, typically small cysts. Participants received the vaccine through a prime-boost schedule consisting of subcutaneous injections during weeks one, three, and five, followed by a booster dose at week 13. Blood samples were collected throughout the study to evaluate immune responses, with optional long-term follow-up visits for immune monitoring.
The primary objectives were to evaluate safety and determine whether the vaccine could generate durable KRAS-specific immune responses.
Results showed the vaccine-induced mutant-KRAS-specific effector and central memory T-cell responses in 90% of participants. These immune responses remained detectable in peripheral blood for 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 Neeha Zaidi, MD, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and corresponding author of the study, in a press release. “In addition, the vaccine was safe and well tolerated, supporting its use in larger cancer interception studies.”
Neeha Zaidi, MD
After a median follow-up of 16.5 months, none of the vaccinated participants developed pancreatic cancer. Investigators also evaluated changes in pancreatic cyst size as an exploratory endpoint and found cyst reduction or resolution in 37.5% of vaccinated participants compared with 6.8% in a similar unvaccinated cohort.
“Overall, this study represents the first proof of concept for the use of vaccines for interception of pancreatic cancer in human patients,” Zaidi added.
Future studies will assess clinical benefit
The investigators cautioned that the study was small and was not designed to determine clinical efficacy.
Michael G. Goggins, MD
“We observed evidence of stability or regression of the pancreatic cysts in association with the induction and durability of KRAS-specific T-cell responses,” said Michael G. Goggins, MD, professor of pathology, medicine, and oncology and the Sol Goldman Professor of Pancreatic Cancer Research at Johns Hopkins University School of Medicine and a senior author of the study, in a press release. “However, larger studies are needed to demonstrate that this effect was in fact due to the vaccine.”
An ongoing trial will further investigate whether vaccine-induced T cells infiltrate precancerous pancreatic tissue in addition to circulating in peripheral blood.
Note: This news summary was generated by AI based on a published press release, followed by a review from human editors.
