Exploring pancreatic cancer vaccines: What’s next?

When most people think of a vaccine, they think of the prevention of a disease. For pancreatic cancer vaccines, though, it’s a little bit different. The vaccines don’t entirely prevent the disease, but they can help prevent it from coming back once someone has been diagnosed and treated.

“People think, ‘I’ve had the cancer removed, I’m cured,’ but even when people have no evidence of disease and have had chemotherapy, the cancer still has a chance of returning,” says gastrointestinal medical oncologist Shubham Pant, M.D. “You achieve the cure by offering something to those patients who don’t have any disease but who are at high risk of reoccurrence.”

In the not-too-distant future, that ‘something’ might be a pancreatic cancer vaccine specific to the mutations in a particular patient’s cancer.

Current treatment options for pancreatic cancer

Patients with pancreatic cancer that hasn’t spread too far beyond the pancreas — that is, stage I through stage III cancers — can have surgery to have the cancer removed. Then, they receive adjuvant chemotherapy to attack the micrometastatic disease, the tiny amounts of cancer that may still exist in the body.

However, even when the cancer seems to be completely gone, 50% to 70% of patients have a relapse within five years. “It’s a very tough cancer,” Pant says.

When pancreatic cancer comes back, there is very little that can be done to treat it. Most of the approaches at that point are palliative, not curative.

How a pancreatic cancer vaccine works

The hope is that a pancreatic cancer vaccine specifically targeted to the mutations in a patient’s cancer cells will be able to prevent a relapse and increase recurrence-free survival. Pant and his colleagues have been testing one called ELI-002, which is targeted toward KRAS G12D and G12R mutations. 

KRAS mutations occur in about 90% of pancreatic cancer cases, and G12D and G12R are commonly mutated in KRAS subtypes. So, if the vaccine is effective, a significant number of patients with pancreatic cancer could benefit.

“What we’re trying to do with these vaccines is to kill the micrometastatic disease further by harnessing the body’s immune system,” Pant says. The idea is that training the immune system to detect and destroy the cancer cells and can potentially prevent cancer recurrence. The body’s immune system will also learn to attack any future cancer cells with these mutations, stopping the cancer before it can grow.

Preliminary results of the vaccine trial

Results from the Phase I trial of the vaccine indicated that T cell responses were seen in 84% of all patients and in 100% of those who received the two highest doses. The patients who had an above-average immune response went a longer period without their cancer returning. This hints that the vaccine is working as intended to train the immune system.

“These were very promising findings,” says Pant, who was the study’s principal investigator.

Furthermore, the side effects profile was very good. This means that patients tolerated the vaccine well, making it safe to administer. Most patients did have some pain and redness at the injection site, similar to what you might experience with other vaccines. More serious side effects were very rare. 

What’s ahead for pancreatic cancer vaccines 

Now that there is data to indicate the pancreatic cancer vaccine is safe and that it does seem to increase T cell response, the next step is to give the vaccine to a larger number of patients to see if it is effective. Patients in the Phase II trial will receive the higher doses that were shown to increase T cell responses in all patients in the Phase I trial, and the vaccine is a slightly different formulation that targets additional KRAS mutations. This will bring the total number of targeted peptides to seven, which collectively affect close to 80% of those who have pancreatic cancer.

Until those results are in, there is no way of knowing what the success rate of the vaccine might be. However, researchers are hopeful.

“I believe that vaccines like this have the potential to improve outcomes in pancreatic cancer,” Pant says.

Learn more about research at MD Anderson.