Even when doctors find pancreatic cancer early enough to remove it with surgery, the disease often comes back within a couple of years. But what if they had a way to keep it from returning?
Two experimental pancreatic cancer vaccines are being tested for that very reason. They aim to train your immune system to seek and destroy the tiniest of cancer cells that might stick around after you get surgery and standard treatments like chemotherapy.
"The hope is that with these vaccines, if we can get the immune system involved more readily controlling the cancer, that we can eliminate more of the microscopic disease before it comes back," says Eric Christenson, MD, a medical oncologist with Johns Hopkins Medicine in Baltimore.
So far, researchers have given the two vaccines to small groups of people in clinical trials. One vaccine uses messenger RNA (mRNA) that's tailored just for you. The other is ready for use as-is, right "off the shelf." Both vaccines target a mutation (change) in the KRAS gene. The mutation may fuel the growth of cells in about 90% of pancreatic cancers that start in the ducts of the pancreas.
Here's a closer look at how the pancreatic cancer vaccines work, what research on them shows, and who can try them.
Personalized mRNA Vaccine for Pancreatic Cancer
The mRNA vaccine is a series of shots called autogene cevumeran (BNT122, RO7198457). It's custom-made based on specific features of your pancreatic cancer tumor.
mRNA is a genetic molecule that instructs cells to make certain proteins. The mRNA vaccine attempts to teach cells in your body to make proteins that trigger an immune system response against multiple proteins that are in your cancer cells. The vaccine is personalized to target the unique proteins found in your specific tumor. KRAS is one of the targets of this vaccine if your tumor has a KRAS mutation. The KRAS gene usually acts like an on-and-off switch that controls cell growth, but mutations can cause the gene to stay turned "on" and make an irregular protein that can cause cells to grow out of control.
"The problem with pancreatic cancer in general is that it has cocooned itself into this rich, dense scar that prevents the immune system from getting in and seeing it as being a problem," Christenson says. But after the mRNA vaccine is injected into your body, it "produces these 'wanted posters' [for the cancer cells] on the surface of lymph nodes." Immune cells that respond to the vaccine learn to recognize the cancer cells and kill them.
A phase 1 clinical trial tested the mRNA vaccine in 16 people with pancreatic cancer who'd gotten surgery. They received the vaccine along with chemo and an immunotherapy drug called a checkpoint inhibitor. The vaccine worked as intended in eight of them, and seven were still alive four to six years after their surgeries. Of the eight people who didn't respond to the vaccine, two were still alive, with a median survival time of almost three-and-half years.
The vaccine caused only mild side effects.
Off-the-Shelf Vaccine for Pancreatic Cancer
The other KRAS-targeted vaccine that's been going through clinical trials is called ELI-002 7P. Unlike the mRNA vaccine, it doesn't have to be made for just one person — it's the same formulation for everyone. "And it's quite easy and straightforward to administer practically in the clinic. It's like getting a flu vaccine in a way," says Eileen M. O'Reilly, MD, a gastrointestinal medical oncologist with Memorial Sloan Kettering Cancer Center in New York, and one of the lead researchers in clinical trials of ELI-002 7P.
A phase 2 trial of the vaccine looked at 144 people with pancreatic cancer who'd gotten surgery and other standard treatments, and showed no visible signs of cancer on imaging tests. Those who were given the vaccine received it after they finished standard treatments. Overall, the vaccine didn't appear to significantly lengthen the time people lived before the cancer came back.
The vaccine maker, Elicio, says that may be partly because 19% of people who got the vaccine had a known risk factor for cancer's return — higher amounts of "residual disease," or lingering cancer cells so tiny, they can only be found with very sensitive lab tests — compared with 10% of those who didn't get the vaccine.
In a more promising finding, people with lower levels of residual disease who got the vaccine lived disease-free for 23.8 months, compared with 12.8 months in those who didn't get the vaccine. So, the researchers want to focus on people with minimal residual disease and look at the effects of giving more vaccine doses in a phase 3 trial.
Side effects included some tiredness, and redness and soreness in the area that was vaccinated. The effects were short-lived and mostly didn't interfere with day-to-day activities, O'Reilly says.
A pancreatic cancer vaccine that doesn't need to be custom-made could have an extra benefit against a disease in which time is often the enemy: It's easier to scale and develop. Once approved, it's ready to go. Compare that to the personalized vaccine, which can take eight to 12 weeks to formulate for an individual, O'Reilly says.
Still, both ELI-002 7P and the personalized mRNA vaccine are "ultimately trying to do the same thing. And they both have shown, preliminarily, that a potent immune response with either can delay cancer coming back," she says.
Patient Eligibility for Pancreatic Cancer Vaccines
So far, clinical trials of the mRNA vaccine and ELI-002 7P have been limited to people with pancreatic cancer that's found early enough to be removed surgically.
"In early stage disease, where you have minimal burden of cancer cells — not evident on a scan, not evident by any blood-based setting — that's probably where immune therapy [with vaccines] is going to have the greatest potential," O'Reilly says. To find out if you're eligible for a clinical trial of a pancreatic cancer vaccine, you can start by checking with your oncologist.
Can These Vaccines Cure Pancreatic Cancer?
That's not clear. Before researchers can even begin to answer that question, they need to do larger clinical trials of the vaccines, which could involve years of follow-up study to track the health of people in the trials.
Clinical trials go through three phases before the FDA considers approving a treatment for use in the general public. If a treatment gets approved, a fourth phase takes an even longer-term look at how effective (and safe) it is.
"We need a lot more [research] for me to feel confident in saying, 'Yes, these are curing people,'" Christenson says of the pancreatic cancer vaccines. But "we hope that [they'll] truly be a curative intervention."
