An mRNA vaccine to treat pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is one of the deadliest types of cancer. Despite modern therapies, only about 12% of people diagnosed with this cancer will be alive five years after treatment.

Immunotherapies, drugs that help the immune system attack tumors, have revolutionized the treatment of many types of tumors. But to date, they have proven ineffective in PDAC. It is unclear whether pancreatic cancer cells produce neoantigens, proteins that can be effectively targeted by the immune system.

An NIH-funded research team led by Dr. Vinod Balachandran of Memorial Sloan Kettering Cancer Center (MSKCC) has developed a personalized vaccine approach for mRNA cancer treatment. It is designed to help immune cells recognize specific neo-antigens on patients’ pancreatic cancer cells. The results of a small clinical trial of their experimental treatment were published on May 10, 2023 in Nature.

After surgery to remove the PDAC, the team sent tumor samples from 19 people to partners at BioNTech, the company that produced one of the COVID-19 mRNA vaccines. BioNTech performed gene sequencing on tumors to find proteins that could trigger an immune response. They then used this information to create a personalized mRNA vaccine for each patient. Each vaccine targeted up to 20 neoantigens.

Personalized vaccines were successfully created for 18 of the 19 study participants. The process, from surgery to administering the first dose of the vaccine, took an average of about nine weeks.

All patients received a medicine called atezolizumab before vaccination. This drug, called an immune checkpoint inhibitor, prevents cancer cells from suppressing the immune system. The vaccine was then given in nine doses over several months. After the first eight doses, study participants were also started on standard chemotherapy drugs for PDAC, followed by a ninth booster dose.

Sixteen volunteers remained healthy enough to receive at least part of the vaccine doses. In half of these patients, the vaccines activated powerful immune cells, called T cells, that can recognize the patient-specific pancreatic cancer. To track the T cells made after vaccination, the research team developed a new computational strategy with Dr. Benjamin Greenbaum’s lab at MSKCC. Their analysis showed that T cells that recognized neo-antigens were not found in the blood prior to vaccination. Of the eight patients with strong immune responses, half had T cells targeting more than one vaccine neoantigen.

A year and a half after treatment, the cancer had not come back in any of the people who had a strong T-cell response to the vaccine. In contrast, among those whose immune systems did not respond to the vaccine, the cancer came back on average just over a year. In one patient with a strong response, the T cells produced by the vaccine even appeared to eliminate a small tumor that had spread to the liver. These results suggest that vaccine-activated T cells have been shown to control pancreatic cancers.

“It’s exciting to see that a personalized vaccine could appeal to the immune system to fight pancreatic cancer, which urgently needs better treatments,” says Balachandran. “It’s also motivating because we may be able to use such personalized vaccines to treat other deadly cancers.”

More work is needed to understand why half of people did not have a strong immune response to their personalized vaccines. Researchers are currently planning to launch a larger clinical trial of the vaccine.

—by Sharon Reynolds