An experimental vaccine designed to prevent pancreatic cancer in people at high risk of developing the disease has shown encouraging early results, with researchers reporting it was safe and generated long-lasting immune responses in most participants.
Results from a Phase I clinical trial, published in the journal Cancer Discovery by the American Association for Cancer Research (AACR), found that the vaccine stimulated a targeted immune response in 90% of participants and no vaccinated patients developed pancreatic cancer during the study’s follow-up period.
Researchers caution, however, that the trial was small and designed primarily to evaluate safety rather than determine whether the vaccine can prevent cancer.
Targeting One of the Deadliest Cancers
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer, largely because it is often diagnosed after it has spread. The disease has a low five-year survival rate, and roughly 10% of cases are linked to inherited genetic mutations that significantly increase a person’s risk.
People with hereditary risk factors or suspicious pancreatic cysts are typically monitored through regular imaging. If physicians believe cancer is developing, surgery is often recommended.
However, according to researchers at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, recurrence rates following surgery can reach 80%, and many precancerous lesions are too small to be detected through imaging.
“Individuals at high risk due to hereditary predisposition or to the presence of a concerning pancreatic lesion detected on imaging usually undergo surveillance to monitor for changes over time,” said Dr. Neeha Zaidi, associate professor of oncology at Johns Hopkins and one of the study’s corresponding authors, AACR reported.
Vaccine Targets Common Genetic Mutations
The experimental vaccine, known as mKRAS-VAX, targets six of the most common mutations in the KRAS gene, which researchers say drive more than 90% of pancreatic ductal adenocarcinomas.
Rather than treating existing cancer, the vaccine is designed to train the immune system to recognize and attack cells carrying KRAS mutations before they develop into invasive cancer.
Researchers enrolled 20 individuals considered at high risk because they had inherited cancer susceptibility genes and imaging had revealed pancreatic lesions, typically small cysts.
Participants received a series of subcutaneous injections over 13 weeks using a prime-and-boost vaccination schedule.
Strong Immune Response Observed
Researchers reported that 90% of participants developed mutant KRAS-specific T-cell immune responses.
Those immune cells remained detectable in participants’ 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,” Zaidi said.
Researchers also reported the vaccine was well tolerated, with no significant safety concerns identified during the trial.
No Cancer Cases During Follow-Up
After a median follow-up period of 16.5 months, none of the vaccinated participants developed pancreatic cancer.
Investigators also examined changes in pancreatic cysts as an exploratory measure.
Among vaccinated participants, 37.5% experienced cyst shrinkage or complete resolution, compared with 6.8% of a similar group of unvaccinated patients.
Researchers emphasized that the study was not designed to prove the vaccine caused those improvements and that larger clinical trials will be needed.
“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 Dr. Michael Goggins, professor of pathology, medicine and oncology at Johns Hopkins, per AACR. “However, larger studies are needed to demonstrate that this effect was in fact due to the vaccine.”
Researchers Call Results a “Proof of Concept”
The investigators described the trial as the first evidence that a vaccine may be capable of intercepting pancreatic cancer before it develops in high-risk patients.
“Overall, this study represents the first proof of concept for the use of vaccines for interception of pancreatic cancer in human patients,” Zaidi said.
Senior researcher Dr. Elizabeth Jaffee said preventing cancer before it develops could have a significant impact for diseases like pancreatic cancer, where early detection remains difficult.
“Prevention and interception save lives and reduce the morbidity associated with cancer development and progression,” Jaffee said, according to AACR. “This is especially important for cancers whose early-onset frequency is increasing and for which we do not have effective methods for early detection.”
Larger Studies Planned
Researchers acknowledged several limitations, including the study’s small size and the lack of a randomized design capable of measuring clinical effectiveness.
An ongoing clinical trial is expected to determine whether vaccine-generated immune cells can penetrate precancerous pancreatic tissue in addition to circulating in the bloodstream.
The study was funded by the National Cancer Institute, the Lustgarten Foundation, and a Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer Research Grant.
If future trials confirm the vaccine’s effectiveness, researchers say it could represent a major advance in preventing one of the world’s deadliest cancers among people at the greatest risk.
Provided by Dallas Express
