mRNA Vaccine Shows Sustained Immune Activity in Small Patient Group

A promising personalized mRNA pancreatic cancer vaccine could potentially beat pancreatic cancer at its own game.

According to a new study published in the journal Nature, the vaccine, dubbed autogene cevumeran, produces what are called durable T cells. Very simply, these T cells are able to do their job of fighting cancer cells that may sporadically pop up for a long period of time.

This is important because pancreatic cancer cells are aggressive, spreading throughout the body much earlier than other cancers. Even when a patient is diagnosed early enough for surgery—the only potential cure for the disease—doctors remain concerned about it recurring. This is because malignant cells that are too small to be picked up by scans may be hiding in other organs. Some estimates show there’s about a 60 to 80 percent chance of recurrence of the disease after surgery.

“The latest data from our phase I trial of personalized RNA vaccines in patients with pancreatic cancer continue to be encouraging,” surgeon–scientist Vinod Balachandran, M.D. of Memorial Sloan Kettering Cancer Center (MSK) (New York, NY), tells Let’s Win. “We see the hallmarks of a robust anti-tumor immune response after vaccination that may potentially last for years in some patients—and this immune response continues to correlate with delayed recurrence,” he adds. Balachandran is the principal investigator of the study and senior author.

New results from the phase I clinical trial show the therapeutic cancer vaccine activated tumor-specific immune cells that persisted in the body up to nearly four years after treatment in some patients. In addition, patients with a vaccine-induced immune response had a reduced risk of the cancer coming back at a three-year follow-up compared with patients whose immune systems did not respond.

Activated T Cell Response Correlates To Delayed Recurrence

The clinical trial involved 16 patients who received the vaccine  along with an immunotherapy drug called atezolizumab and the mFOLFIRINOX chemotherapy regimen. Early immunological and clinical results from a trial published in Nature in 2023 showed this treatment was generally well tolerated and stimulated an immune response that correlated with delayed recurrence at a 1.5-year median follow-up compared with nonresponders.

The latest paper reports results at a three-year median follow-up and show: 

• The investigational cancer vaccine activated a T cell response in half of patients (eight responders), and this response correlated with delayed recurrence at three-year post-treatment follow-up compared with nonresponders. Researchers do not yet know if the vaccine caused the delay in cancer recurrence; investigating this question is a goal of an ongoing randomized phase II clinical trial.
• Of the eight patients whose immune systems responded to the vaccine during the study period, six have not seen their cancers return during the follow-up period. The other two patients relapsed. Those patients with relapse showed weaker vaccine-induced T cell activity compared with other responders.
• By studying tissue and blood from these patients before and after the vaccine was given, the team found that the majority of T cells had been newly stimulated by the vaccine, as these T cells were undetectable before vaccination. In addition, the majority of these vaccine-induced T cells persisted beyond two years post-vaccination and maintained anticancer function in some patients.

“These promising results, however, remain early and in a small number of patients,” notes Balachandran, director of The Olayan Center for Cancer Vaccines at MSK. Broader testing in a larger number of patients is currently ongoing in a global randomized phase II trial.

“For patients with pancreatic cancer, our latest results continue to support the approach of using personalized mRNA vaccines to target neoantigens in each patient’s tumor,” Balachandran explains. “If you can do this in pancreas cancer, theoretically you may be able to develop therapeutic vaccines for other cancer types.”

Let’s Win will continue to cover further developments of this promising vaccine.