mRNA Pancreatic Cancer Vaccine Trial Heading for Phase II

Silver linings are rare, especially when it concerns the COVID-19 pandemic.

However, if there is a silver lining to be found, it is the commercial development of the mRNA vaccines, which changed the trajectory of the disease. The scientific community combined their efforts globally to create COVID-19 vaccines in a timeframe that at first seemed impossible. But the vaccines became available to the public in less than a year, due, in no small part, to the groundwork on mRNA vaccines that had been done over the last 30 years.

How does this relate to pancreatic cancer? mRNA vaccines were originally thought to be a potential tool against diseases like cancer. Today, that thought may be edging toward reality.

Let’s Win reported results of a pancreatic cancer mRNA vaccine trial presented at the American Society of Clinical Oncology conference in 2022. The treatment was developed by Vinod Balachandran, M.D., of the Memorial Sloan Kettering Cancer Center (MSKCC) in New York City, working together with the biopharmaceutical firm BioNTech and the biotechnology company Genentech.

Updated results from the phase I trial were reported in the May 10, 2023 issue of the journal Nature. Those results suggest that personalized pancreatic cancer vaccines cause an effective and lasting immune response to the disease, potentially delaying its relapse.

“We are encouraged by the results (and) we look forward to testing individualized mRNA vaccines now in more pancreatic cancer patients,” says Balachandran, a surgeon–scientist in the Human Oncology and Pathogenesis Program at MSKCC and a member of the David M. Rubenstein Center for Pancreatic Research.

Some studies suggest that most cases of pancreatic cancer harbor increased levels of neoantigens. These neoantigens are cell-surface proteins that can emerge on the surface of tumors following certain types of DNA mutations. The hope is that these neoantigens can be targeted by personalized vaccine therapies with the aim of boosting the immune system’s T cell activity and improving outcomes.

Promising Results in Phase I

In the phase I clinical trial, Balachandran and colleagues administered personalized mRNA vaccines called adjuvant autogene cevumeran in combination with chemotherapy and immunotherapy in 16 patients with pancreatic cancer.

Within a year and a half of completing the treatment, the cancer had not returned in half of the participants, each of whom had a strong T cell response to the vaccine. In contrast, among the remaining eight participants whose immune systems did not respond to the vaccine, the cancer recurred within an average of 13 months. In one patient with a strong response, T cells produced by the vaccine even appeared to eliminate a small tumor that had spread to the liver. These results suggest that the T cells activated by the vaccines kept the pancreatic cancer in check.

A Theory Worth Investigating

The researchers have a theory about the non-responder group. “We think the spleen might be important to generate a strong immune response to this particular vaccine,” Balachandran says, adding that several non-responders previously had routine splenectomies (spleen removal) as part of their pancreatic cancer surgery. That hypothesis, he says, requires further testing.

A larger, randomized clinical trial involving patients at multiple sites in various countries is set to open in summer 2023.  Patient participants will be required.

Let’s Win will keep you updated on the trial once enrollment begins.