mRNA Vaccine Targeting Pancreatic Cancer Shows Promise in New Study of Clinical Trial

Personalised mRNA vaccines have shown promise as pancreatic cancer treatment in a phase-1 clinical trial, published in the journal Nature. Less than 13 per cent of those diagnosed with pancreatic cancer - difficult to diagnose early because it does not always have obvious symptoms, live for more than five years, making it one of the deadliest types of cancer.

According to experts, it happens because more than 95 per cent of the 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 spread only when the original tumours become large. The disease typically does not cause many symptoms until later stages and there is no routine screening for pancreatic cancer like a mammogram or colonoscopy.

Once it gets diagnosed, there are very 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 on 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 per cent despite our best current treatments.”

That highlights the desperate need for more options, he said.

Before mRNA vaccines became widely used for COVID-19, researchers had already been developing the technology for cancer treatment. It teaches a person’s immune system to recognise and attack tumours, turning it into a cancer-fighting machine.

mRNA technology is currently being explored for melanoma and colorectal cancer, along with other solid tumours.

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. According to experts, these T cells 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 extremely high.

For a vaccine to teach the body to recognise tumours, it has to be targeted on those tumour cells that are unique—which means that they should not appear anywhere else in the body. Since tumours are created from mutations, these mutations, expressed as proteins on the surface of cancer cells, serve as targets.

Pancreatic cancers typically do not have many targets to choose from.

It is popularly believed that this lack of mutations—serving as targets for an mRNA cancer vaccine—would make pancreatic cancer a poor choice for the therapy. However, the study has proved that this assumption may be wrong. The trial was a longer follow-up to an initial 2023 trial—which had first tested the efficacy of the vaccines in a subset of those with pancreatic cancer.

According to the scientists, the new trial included 16 patients with pancreatic cancer—who had tumours that could be removed in surgery. Experts said this is a relatively rare occurrence in pancreatic cancer, as only 20 per cent of this cancer is operable—the only treatment to stop it. Chemotherapy, radiation, and immunotherapies do shrink tumours or keep them from growing but are not considered cures.

Balachandran and his team followed the patients in the trial for up to four years. The participants first had their tumours removed sometime between 2019 and 2021. Then, the team used genetic material from each person’s tumours to design perso mRNA vaccines they hoped would teach the patient’s immune systems to attack their cancer cells.

In addition to the vaccine, all 16 people were also treated with the current standard of care which included surgery, chemotherapy, and an immunotherapy drug called atezolizumab. Half of those in the trials responded to the vaccine, producing T cells that targeted their tumours. However, the others did not respond to the vaccine.

In those 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 per cent of the T cells could potentially survive and function for decades.

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