Pancreatic cancer is one of the deadliest forms of cancer, with fewer than 13% of patients surviving more than five years after diagnosis. This grim statistic is largely due to the fact that the disease is often detected too late. “Around 90% of cases are diagnosed when the disease is already advanced,” according to Dr. Vinod Balachandran, director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering Cancer Center. Unlike other cancers with routine screening tests, such as mammograms for breast cancer or colonoscopies for colorectal cancer, pancreatic cancer lacks a widely available early detection method.
One of the unique and troubling aspects of pancreatic cancer is its ability to spread rapidly. “Pancreatic cancer cells also spread to other parts of the body much earlier on than in other cancers, which typically spread only when the original tumors are large,” Balachandran noted. By the time symptoms like jaundice, weight loss, or abdominal pain appear, the disease is often in an advanced stage, limiting treatment options.
Current treatments for pancreatic cancer include surgery, chemotherapy, radiation, and immunotherapy. However, even with these methods, the prognosis remains poor. Surgery is the only potential cure, yet only 20% of cases are operable at the time of diagnosis. For those lucky enough to undergo surgery, the cancer frequently returns. “Although we have made significant progress in improving outcomes in many of the other cancers with newer waves of cancer treatments, these have not had much of an impact in pancreatic cancer,” Balachandran said. “Survival rate has remained about 10% despite our best current treatments.”
The Science Behind mRNA and Cancer Vaccines
mRNA vaccines, which gained global recognition during the COVID-19 pandemic, are now being explored as a revolutionary treatment for cancer. These vaccines work by teaching the immune system to recognize and attack specific proteins. While this approach has proven highly effective against viruses, using it to fight cancer presents unique challenges. Cancer cells originate within the body, making them harder for the immune system to identify as threats.
To be effective, mRNA cancer vaccines must stimulate the production of large numbers of T cells, which are immune cells that recognize and destroy cancerous cells. However, these T cells must also persist long-term in the body to provide lasting protection against recurrence. “While this is a relatively straightforward feat when it comes to viruses, teaching a person’s T cells to fight nonforeign cells that their body itself made is much more difficult,” the study explained. Pancreatic cancer poses an even greater challenge because it has fewer unique mutations than other cancers, making it harder to find effective targets for a vaccine.
Despite these challenges, researchers have discovered that pancreatic cancer may be a more viable target for mRNA vaccines than previously thought. This insight led to a groundbreaking clinical trial aimed at testing the feasibility of personalized mRNA vaccines for pancreatic cancer.
Promising Research and Early Results
A phase 1 clinical trial, led by Balachandran at Memorial Sloan Kettering Cancer Center, has demonstrated that mRNA vaccines can indeed stimulate the immune system to fight pancreatic cancer. The study involved 16 patients who had undergone surgery to remove their tumors. Each patient received a personalized mRNA vaccine tailored to their specific tumor’s genetic makeup, along with chemotherapy and an immunotherapy drug called atezolizumab.
The results were encouraging. Half of the participants (8 out of 16) developed a strong immune response, producing cancer-fighting T cells that targeted their tumors. “The fact that they were able to use a vaccine to generate a response to new mutations that come up in the tumors, and then were able to show that this subsists, is promising,” said Dr. Brian Wolpin, director of the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute.
The trial also examined how long the immune response lasted. Researchers estimated that the cancer-fighting T cells generated by the vaccine could persist for nearly eight years, with some potentially remaining active for decades. “You have to take this with a little perspective, this is not treating hundreds of thousands of people,” Wolpin cautioned. “But if we can see this response stand up in bigger trials, that’s really significant.”
Longer-term follow-ups provided further insight. In the three years following treatment, only two of the eight vaccine-responsive patients experienced a cancer recurrence, compared to seven of the eight non-responders. These results strongly suggest that the vaccine is helping prevent the return of pancreatic cancer. “This gives us a little more confidence that once you get a T cell response, that it could be durable, it’s not a shock response,” said Dr. Shubham Pant of the University of Texas MD Anderson Cancer Center.
What This Means for the Future
If further trials confirm these findings, mRNA vaccines could revolutionize pancreatic cancer treatment. By generating a long-lasting immune response, the vaccine could not only fight existing cancer cells but also prevent recurrence. This is crucial, as pancreatic cancer often spreads undetected to other organs before diagnosis.
A larger clinical trial is now underway to validate these early results. Researchers are also exploring “off-the-shelf” mRNA vaccines that target common mutations found in pancreatic cancer, such as the KRAS mutation, which occurs in 90% of cases. Unlike personalized vaccines, these could be mass-produced and administered more quickly.
A New Hope for Pancreatic Cancer Patients
For patients like Barbara Brigham, who participated in the clinical trial, the vaccine has already provided hope and extended survival. Diagnosed in 2020, Brigham has remained cancer-free for over four years—well beyond the typical prognosis for pancreatic cancer. “The trial was such a wondrous thing,” she said. “It has just given me such a renewal in my life.”
Despite the promising results, researchers caution that this is still an early-stage study. “It’s still hard to attribute causality” to the vaccine, said Dr. Suneel Kamath, a gastrointestinal oncologist at the Cleveland Clinic. However, he emphasized that the study provides an important “proof of concept” that mRNA vaccines can create a durable immune response against pancreatic cancer.
Pancreatic cancer remains one of the most difficult cancers to treat, but this research suggests that a future where patients live longer—and perhaps even achieve remission—is within reach. As scientists continue to refine mRNA technology, it could become a powerful weapon against not only pancreatic cancer but also other hard-to-treat cancers. “Hopefully this can provide some important lessons and clues and how we can do this in other cancer types,” Balachandran said.
For now, cautious optimism prevails. If future trials confirm the durability and effectiveness of this approach, mRNA vaccines could finally turn the tide against one of the deadliest cancers known to medicine.
