Vaccine to prevent pancreatic cancer passes first test in humans
Early trial data show it's safe, triggers intended anticancer response
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An anticancer vaccine targeting a common genetic driver of pancreatic cancer was shown to be safe in an early clinical trial, with the results also suggesting it triggered the intended immune response and could potentially intercept the disease.
According to the researchers, the experimental vaccine is designed to generate an immune response against a protein called KRAS, which helps regulate cell growth and is thought to play a key role in pancreatic cancer’s development. Data showed that none of the participants in the small trial had developed pancreatic cancer or any lesions requiring surgery after more than a year.
Although the scientists stressed that more testing is needed, these first-in-human findings suggest that the vaccine candidate may help prevent pancreatic cancer in high-risk individuals, the team noted.
“We have more work to do, but this is a good start aimed at prevention, which no one had thought about doing before,” Elizabeth Jaffee, MD, coauthor of the study and deputy director of the Johns Hopkins Kimmel Cancer Center in Baltimore, said in a university news story detailing the findings.
The study, titled “First-in-human testing of a mutant KRAS vaccine for pancreatic cancer interception in high-risk cohorts,” was published in the journal Cancer Discovery by a team from several U.S. institutions. The work was funded by the National Institutes of Health, Stand Up To Cancer, a U.S.-based nonprofit, and the Lustgarten Foundation, a major backer of pancreatic research.
PDAC, or pancreatic ductal adenocarcinoma, is the most common form of pancreatic cancer. Usually, overt PDAC develops out of precancerous lesions or cysts in the pancreas, a gland in the upper abdomen that aids digestion and helps regulate blood sugar. As such, it’s theoretically possible to prevent PDAC by targeting these lesions, or areas of tissue damage.
Still, actually identifying and effectively treating them, without causing excessive damage to healthy parts of the pancreas, remains a challenge.
Testing a potential pancreatic cancer vaccine for safety, effectiveness
Almost all PDAC tumors carry mutations that affect the KRAS protein. Cancer-driving mutations in this protein can prompt cells to grow more than they should, ultimately leading to tumor formation. KRAS mutations are also present in many precancerous lesions in the pancreas, suggesting it might be possible to target these early lesions by targeting this cancer-associated mutation.
Designed for prevention, vaccines work by teaching the immune system how to effectively attack a specific molecular target, such as a piece of an infectious virus or bacteria. Here, researchers designed a vaccine called mKRAS-VAX, which aims to trigger an immune attack targeting the six most common KRAS mutations.
The idea is that the immune system could eliminate cells in precancerous lesions that carry these mutations, effectively preventing pancreatic cancer from developing, according to the researchers.
“The ability to vaccinate people at risk early to try to prevent them from developing cancer in the future is an important opportunity,” Jaffee said.
An earlier study tested the mKRAS-VAX vaccine in people with PDAC whose lesions had been surgically removed but were at high risk of recurrence. The results suggested that the vaccine can trigger a strong immune response, as designed.
Trial enrolled people at high risk of PDAC, the most common type
This new trial enrolled 20 people who were at high risk of PDAC. Specifically, all of the participants carried genetic variants linked to an increased likelihood of developing this type of cancer, and all also had abnormalities on imaging of the pancreas that can indicate precancerous lesions.
“We thought if we can see an immune response in patients with cancer, the vaccine should work even better in people who are at higher risk because of a family history, gene alteration or cyst on the pancreas,” said Neeha Zaidi, MD, also a coauthor and a professor of oncology at Johns Hopkins.
Each participant received four doses of the mKRAS-VAX vaccine, administered over 13 weeks, or about three months. The trial’s main goal was to establish the safety profile of the mKRAS-VAX vaccine, and results were generally positive.
No serious side effects were reported, and those that did occur resolved without medical intervention, the researchers noted. The most common side effects were injection-site reactions, fatigue, chills, and flu-like symptoms — all of which can be commonly caused by any vaccine that activates the immune system.
This is just the beginning, but the findings suggest that the immune system is getting activated.
Data from the trial also suggested that the mKRAS-VAX vaccine triggered an immune attack against mutant KRAS as designed. Specifically, the researchers examined the activity of T-cells, which are immune cells that can kill cancer cells. In 18 of the 20 trial participants, T-cell responses against mutant KRAS were significantly elevated, with a median 18.2 times increase.
Available imaging data showed that pancreatic cysts decreased or resolved entirely in eight participants, and over a median follow-up of more than a year, none developed overt PDAC. The researchers stressed that it’s not possible to draw any definitive conclusions about efficacy from this small study, but they said the results “support the advancement of [the mKRAS-VAX vaccine] for PDAC interception.”
According to Jaffee, “this is just the beginning, but the findings suggest that the immune system is getting activated.”
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