“Pancreatic cancer is very, very challenging, with a poor five-year survival rate of 13 percent,” says the trial investigator Neeha Zaidi, MD, an associate professor of oncology at the Johns Hopkins School of Medicine’s Sidney Kimmel Comprehensive Cancer Center in Baltimore. “Most of the time, people don’t have symptoms until it’s quite advanced,” she says. Once the cancer has reached later stages, treatment options are limited.
The goal of the new vaccine is to stop the cancer before it starts, Dr. Zaidi explains. While the clinical trial results are early, no participants given the vaccine developed pancreatic cancer, despite being at high risk for the disease.
“This is the type of innovation that is urgently needed in people at high risk of pancreatic cancer,” says Peter Hosein, MD, an associate director for clinical research at Sylvester Comprehensive Cancer Center’s Pancreatic Cancer Research Institute in Miami, who was not involved in developing the new vaccine.
Pancreatic Cancer Vaccine Targets Specific Genetic Mutations
Researchers designed the vaccine to prevent pancreatic ductal adenocarcinoma, the most common and aggressive form of pancreatic cancer. About 10 percent of cases are linked with a genetic predisposition. The disease starts with lesions and neoplasms, or precancerous cysts. But even if these cysts are removed with surgery, the chance they’ll come back is up to 80 percent. These lesions can also be microscopic and difficult to detect.
The vaccine is meant to target mutations related to the cancer. More than 90 percent of pancreatic ductal adenocarcinomas occur because of mutations in the KRAS gene. The vaccine, called the mKRAS-VAX, targets six of the most common KRAS mutations found in pancreatic ductal adenocarcinomas and in most pancreatic precancerous lesions.
In the phase 1 clinical trial, researchers administered the vaccine to 20 high-risk adults with evidence of a pancreatic lesion or cyst. Participants received vaccine doses at weeks 1, 3, and 5, followed by a booster dose at week 13. They also did blood tests and follow-up visits to monitor their immune system.
The researchers found that the vaccine stimulated a molecule that can turn off the mutated KRAS genes that can lead to pancreatic cancer. The vaccine also activated the immune system’s T cells, white blood cells that detect cancerous lesions, in 90 percent of participants. The researchers still detected this response in participants’ blood two years after vaccination.
After a follow-up of about 16.5 months, none of the participants had developed pancreatic cancer. Vaccinated participants had cysts that shrank or disappeared at a higher rate, about 38 percent, than those of an unvaccinated group that saw cyst reductions of around 6.8 percent.
The Results Are Very Preliminary and Come With Caveats
This was a small clinical trial, and the follow-up period was short. The researchers also relied on blood tests to measure immune changes, but didn’t analyze precancerous tissue.
Still, this phase 1 trial was designed to test safety and determine whether the vaccine sparked an immune response in humans. It passed both those tests, Zaidi says. She points out that the trial found the vaccine to be “incredibly safe,” with patients only experiencing typical vaccine side effects, such as injection site reactions and flu-like symptoms.
“We need larger studies that are designed to look at certain endpoints,” Zaidi says. “But we needed to start somewhere.”
Findings Provide Hope to Patients and Cancer Researchers
Pancreatic cancer is a difficult disease to have, Dr. Hosein says. “Once diagnosed, it is generally resistant to treatment, and patients often decline rapidly,” he says.
While Hosein says some progress has been made in treating people considered high risk, that’s largely due to regular screenings. “The holy grail in these patients is to intercept cancer and prevent it from happening in the first place,” he says.
The vaccine is a “promising strategy” to prevent pancreatic cancer, according to Jaekyung Cheon, MD, an oncologist in the gastroenterology oncology program at Moffitt Cancer Center in Tampa, Florida, who was not involved in the vaccine’s development. “These findings are encouraging because most pancreatic cancer research has focused on treating advanced disease, whereas this study explores a preventive approach for high-risk individuals,” she says.
What Happens Next
The vaccine is currently being tested in a different group of high-risk adults. This group will receive the vaccine before having surgery to remove precancerous lesions. Researchers will analyze the lesions to determine whether the vaccine-generated T cells actually infiltrate the risky tissues, Zaidi says.
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