Personalized mRNA vaccines show promise as pancreatic cancer treatment, a phase 1 clinical trial published Wednesday in Nature found.
Fewer than 13% of people diagnosed with pancreatic cancer live for more than five years, making it one of the deadliest types of cancer. That is, in part, because around 90% of cases are diagnosed when the disease is already advanced.
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. The disease typically doesn’t cause symptoms until later stages and there isn’t a routine screening for this cancer, such as a mammogram or colonoscopy.
Once it’s detected, there are few effective treatments.
“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,” said Dr. Vinod Balachandran, director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering Cancer Center, who led the trial. “Survival rate has remained about 10% despite our best current treatments.”
That highlights the desperate need for more options, he said,
Before mRNA vaccines became widely used for Covid, researchers had already been developing the technology for cancer treatment. This version of the vaccines teaches a person’s immune system to recognize and attack tumors, turning the immune system into a cancer-fighting machine. mRNA technology is currently being explored for melanoma and colorectal cancer and other solid tumors.
To be effective, mRNA cancer vaccines have to produce a lot of T cells, a type of immune cell that protects the body against invaders. These T cells also need to last a long time in cancer patients and retain their ability to detect and fight off cancer cells. 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.
For pancreatic cancer, the task is monumental.
For a vaccine to teach the body to recognize tumors, there have to be targets on those tumor cells that are unique, meaning they don’t appear elsewhere in the body. Since tumors are created from mutations, these mutations, expressed as proteins on the surface of cancer cells, serve as the targets. Pancreatic cancers typically do not have many targets to choose from.
It’s been a widespread belief that this lack of mutations, which serve as targets for an mRNA cancer vaccine, would make pancreatic cancer a poor choice for the therapy. But the new study showed that assumption may be wrong.
The trial was a longer follow-up to an initial 2023 trial that first tested the efficacy of the vaccines in a subset of people with pancreatic cancer. Phase 1 clinical trials are very early stages of research and are meant to determine whether a certain treatment is safe and shows promise of efficacy.
The new trial included 16 patients with receptacle pancreatic cancer, meaning a surgeon can remove the tumors. This is a relatively rare occurrence in pancreatic cancer — only about 20% of pancreatic cancers are operable, which is the only treatment that can stop this type of cancer. Chemotherapy, radiation and immunotherapies can shrink tumors or keep them from growing, but are not considered cures. In an even smaller percentage of people, surgery is possible without first shrinking the tumors with chemotherapy, Wolpin said. The cancer returns about half of the time.
Balachandran and his team followed the 16 patients in the trial for up to four years. The participants first had their tumors removed sometime between 2019 and 2021. Then, the team used genetic material from each person’s tumors to design personalized mRNA vaccines they hoped would teach the patients’ immune systems to attack their cancer cells.
In addition to the vaccine, all 16 people were also treated with the current standard of care — surgery, chemotherapy and an immunotherapy drug called atezolizumab.
Half of the people in the study — eight of the participants — responded to the vaccine, producing T cells that targeted their tumors. The other half didn’t respond to the vaccine.
One of the most important aspects of using a person’s immune system to fight their cancer is ensuring their response —in this case, the cancer-fighting T cells — have longevity. That way, they stay in the body, fighting off cancer cells that pop up, rather than only working for a short amount of time.
In the people in the trial who did mount a response, the vaccine would give their cancer-fighting T cells an average lifespan of nearly eight years, the researchers estimated. They believe that about 20% of the T cells could potentially survive and function for decades. The longer the T cells survive, the better to protect against the cancer’s return.
Early trials are meant to test whether or not a treatment is feasible — in this case, if an mRNA vaccine for pancreatic cancer could produce durable T cells.
The findings suggest that it can. However, it’s still unknown whether these T cells will extend a person’s life and if so, by how much –– that is a task for the next phases of trials. Just two of the patients who had a response to the vaccine had their cancer return during the three-year follow- up, compared to seven of the eight who did not respond to the vaccine treatments.
“You have to take this with a little perspective, this is not treating hundreds of thousands of people,” said Dr. Brian Wolpin, director of the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. “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.”
Because pancreatic cancer cells are adept at spreading early on, some organs may be harboring undetectable cancer cells that don’t show up on scans, meaning these tumors aren’t treated.
With vaccines, the immune system may be able to kill these cancer cells, as well as new ones that pop up, said Dr. Shubham Pant, a professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center.
Very early on in pancreatic cancer development, “cells can escape and set up shop somewhere else –– in the liver or in the lungs. They may be quietly sitting in those other organs and then come back,” he said.
Despite the caveat of being a small group of patients and a very early trial, Pant said, the results are encouraging.
Other research teams, including scientists at MD Anderson, are working on off-the-shelf mRNA vaccines for pancreatic cancer, meaning the vaccines have a target that is common in all pancreatic cancer tumors, rather than a personalized target based on a person’s individual tumor.
About 90% of pancreatic cancer cases include a mutation called KRAS, meaning nonpersonalized vaccines, which could be produced in bulk and would not require a piece of a person’s tumor to create, could potentially be another option down the road. (These vaccines are also currently in very early stages of research).
“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,” Pant said. “If we can see this response stand up in bigger trials, that’s really significant.”
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