An mRNA cancer vaccine may offer long-term protection 

A new mRNA vaccine could prevent pancreatic cancer from returning — potentially for the long haul.

In a small clinical trial, some patients who received the vaccine remained cancer-free for more than three years, researchers reported February 19 in Nature.

That is “pretty remarkable,” says Aaron Sasson, who directs the Pancreatic Cancer Center at Stony Brook Medicine in New York and was not involved with the work. Despite facing a notoriously lethal cancer, these patients lived “a lot longer than we would have otherwise expected,” he says.

The new research, which is still in the proof-of-concept stage, suggests that a cancer vaccine strategy could one day offer patients a long-lasting treatment option. 

The results come amid recent news that officials at the National Institutes of Health are telling scientists to avoid mentioning mRNA vaccine technology in grant applications. It’s a move that could significantly hamper the advancement of mRNA vaccines in cancer research and patient care, Sasson says.

Unlike a traditional vaccine — such as the annual flu shot — which helps our bodies ready defenses for future viral encounters, this type of cancer vaccine acts therapeutically, after someone has already developed cancer. It works by teaching patients’ immune cells what pancreatic cancer looks like. Those educated cells can then seek out and destroy tumors. This approach is part of a growing field of cancer immunotherapies that enlist people’s own immune systems in treatment.

Dozens of similar cancer vaccines are in the works. Researchers are testing the new mRNA cancer vaccine in melanoma and colorectal cancer as well as other vaccines in even more cancers. Excitement about this technology has been brewing in the cancer vaccine field, says Vinod Balachandran, a surgical oncologist at Memorial Sloan Kettering Cancer Center in New York City who led the recent pancreatic cancer vaccine trial.

He hopes the work could offer a blueprint for developing effective vaccines against even more types of cancer. Science News spoke with Balachandran and Sasson to understand how cancer vaccines work, the future of the field and why some researchers are focusing on pancreatic cancer.

We need more therapies for pancreatic cancer 

Doctors already have a set of therapies for treating pancreatic cancer. The problem is, they just don’t work very well, Sasson says. “A lack of effective therapy has really plagued the field.”

Diagnosing pancreatic cancer can be tricky; it kills more than 450,000 people globally every year, so patients often learn they have the disease at an advanced stage. The pancreas is a flattened, pear-shaped gland tucked away inside the body, behind the stomach. That makes it difficult for doctors to manually check for lumps, unlike breast cancer. And some symptoms, such as weight loss and fatigue, aren’t obvious clues that someone has the disease.

Current treatment options include surgery, chemotherapy, radiation therapy and drugs that attack cancer cells. Nevertheless, the five-year survival rate for pancreatic cancer is around 13 percent, meaning that five years after diagnosis, 87 out of 100 patients will have died.

“If you’re diagnosed with pancreas cancer,” Sasson says, “the odds are extremely high you’re going to die from pancreas cancer.”

Cancer vaccines harness the power of the immune system

Cancer vaccines may extend patients’ lives and are part of an expanding class of therapies that harness our bodies’ own defenses to fight disease. The U.S. Food and Drug Administration has already approved dozens of such immunotherapies, including checkpoint inhibitors, which rev up the immune system; therapeutic antibodies, which help the immune system spot cancer; and T-cell transfer therapy, which involves supercharging a patient’s own immune cells.

The common thread here is the immune system, Sasson says. “Our immune system is a very, very efficient killing machine.”

Cancer vaccines like the one Balachandran’s team is testing, which was jointly developed by the biotechnology companies BioNTech and Genentech, take a different approach. They show patients’ bodies a tiny, nonfunctional piece of their tumor, serving as a Bat-Signal for the immune system. In response, the body produces immune cells called T cells that can recognize cancer as something that’s not supposed to be there — something that’s to be destroyed.

RNA cancer vaccines use some of the same technology as COVID vaccines 

The cancer vaccine works similarly to mRNA COVID-19 vaccines, but instead contains instructions for building cancer proteins rather than coronavirus proteins and is given after the disease develops, rather than before. There’s another major difference: The cancer vaccine is personalized for every patient.

“Each individual tumor has a unique combination of genetic mutations,” Balachandran says. To create the vaccine, doctors first surgically remove a patient’s tumor and analyze its DNA for genetic errors. Some of these errors produce mutant tumor proteins, which the immune system can recognize like red flags warning danger. Patients receive a personalized vaccine containing RNA sequences that encode those red flags, Balachandran says.

This process teaches patients’ immune systems to be on the lookout; when immune cells see the red flags, they know it’s time to strike. Your body makes “these cells that can recognize the cancer, kill the cancer, and last in the body for long periods of time” in case the cancer ever comes back, Balachandran says.

An effective cancer vaccine needs to be long-lasting

In a small clinical trial involving pancreatic cancer patients, the vaccine spurred a strong immune response in eight out of 16 participants, generating a legion of red flag–targeting T cells. Balachandran’s team reported those results in 2023. At the time, the prevailing wisdom was that “you could not teach the immune system to recognize pancreatic cancer,” he says.

Many scientists thought pancreatic cancer did not create enough red flags to alert the immune system. The team’s results challenged that view. Scientists now know that the cancer produces these red flags — and they can identify them, build a vaccine around them and use that vaccine to grow an army of T cells that hunt for pancreatic cancer.

But an effective cancer vaccine requires more, Balachandran says. “Not only do you need to make the cells, but the cells need to last and retain function long-term.” His team followed the 16 patients for up to about four years; all had undergone surgery and subsequently received an immune checkpoint inhibitor, their personalized vaccine and a standard chemotherapy regimen. Of the eight people who mounted an immune response to the vaccine, only two saw their cancers return. In contrast, seven of the eight who did not respond saw their cancer return after about a year.

“It’s a big deal,” Sasson says, because it suggests the vaccine can generate immune cells that patrol the body like guard dogs even several years later.

Balachandran can’t say for sure why the vaccine didn’t work for everybody, though it’s possible the spleen may be involved. Some patients had their spleens removed prior to vaccination. The organ is part of the immune system and helps generate immune responses. Without it, the immune response to the vaccine may be weaker.

He and his colleagues are now enrolling patients at Memorial Sloan Kettering and other sites around the world in a larger trial to test whether the vaccine is safe and effective.