Personalized mRNA Vaccine Shows Promise Against Aggressive Pancreatic Cancer

In a small trial, the vaccine prompted a considerable immune response, offering hope to people with this often deadly cancer.

A personalized mRNA vaccine against an aggressive form of pancreatic cancer has shown early promise in a phase 1 clinical trial, where it was found to induce a significant immune response and potentially delay relapse.

When used in combination with chemotherapy and immunotherapy, the individualized vaccine – called adjuvant autogene cevumeran – triggered a substantial T cell response in half of the patients. Remarkably, 18 months later, none of these individuals showed signs of cancer progression, whereas, in the group that did not respond to the vaccine, median time to recurrence was 13.4 months.

This, it is hoped, could open up a new and much-needed therapeutic avenue for a notoriously aggressive and difficult-to-treat form of pancreatic cancer: pancreatic ductal adenocarcinoma (PDAC).

PDAC is the third largest cause of cancer death in the US and is lethal in 88 percent of patients. Current treatments include surgeries and medicines, but these have had limited success. 

One type of immunotherapy that has gained traction in recent years, revolutionizing cancer treatment, involves drugs known as immune-checkpoint inhibitors (ICIs). ICIs work by directing the immune system toward mutated proteins, called neoantigens, that can emerge on the surface of tumors. Unfortunately, pancreatic cancers generally don’t respond to this type of treatment.

The latest trial, which is the subject of a newly published paper, challenges this by demonstrating that T cells specific to PDAC neoantigens can in fact be activated by an individualized mRNA vaccine.

“[The authors] have established the feasibility of using mRNA-based neoantigen vaccines for pancreatic cancer, a disease that has previously been considered too aggressive for personalized therapeutics,” concludes a News & Views article accompanying the study.

“The data also highlight the potency of pancreatic cancer neoantigens, giving hope that they might lead to the development of new treatment options for this refractory cancer.”

In the trial, 16 individuals with PDAC underwent surgery to remove their tumors. Using these resected tumors, the team tailor-made mRNA vaccines containing neoantigens specific to each individual. Nine weeks after surgery, the vaccines were administered alongside an immunotherapy called atezolizumab and, four weeks later, chemotherapy.

“Despite the limited sample size, these early results warrant larger studies of individualized mRNA neoantigen vaccines in PDAC,” the authors write in their discussion.

And hopefully, we won’t have to wait too long for the results: a follow-up trial is imminent, they add.

Personalized mRNA vaccines have previously shown promise in trials for skin cancer, as well as head and neck cancers.

The study is published in Nature, along with a companion News & Views article.

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