Pancreatic cancer vaccine shows promise in small trial

Five years ago, a small group of cancer scientists gathered at a restaurant in a desecrated church hospital in Mainz, Germany, and hatched a daring plan: They would test their new cancer vaccine against one of the most virulent forms of the disease, a cancer patient. . notorious for roaring, even in patients whose tumors had been removed.

The vaccine may not stop that relapse, some scientists thought. But patients were desperate. And the speed with which the disease, pancreatic cancer, often returned could work in the scientists’ favor: For better or for worse, they would soon discover whether the vaccine helped.

Wednesday the scientists reported results that defied the long odds. The vaccine triggered an immune response in half of the patients treated, and those people did not show a relapse of their cancer over the course of the study, a finding described by outside experts as extremely promising.

The study, published in Nature, was a milestone in the long-standing movement to create cancer vaccines tailored to individual patients’ tumors.

Researchers at Memorial Sloan Kettering Cancer Center in New York, led by Dr. Vinod Balachandran, extracted patients’ tumors and sent samples to Germany. There, scientists from BioNTech, the company that made a very successful Covid vaccine with Pfizer, analyzed the genetic composition of certain proteins on the surface of the cancer cells.

Using that genetic data, BioNTech scientists then produced personalized vaccines designed to teach each patient’s immune system to attack the tumors. Like BioNTech’s Covid injections, the cancer vaccines relied on messenger RNA. In this case, the vaccines instructed the patients’ cells to make some of the same proteins found on their excised tumors, potentially triggering an immune response that would come in handy against actual cancer cells.

“This is the first demonstrable success – and I will call it a success, despite the preliminary nature of the study – of an mRNA vaccine in pancreatic cancer,” said Dr. Anirban Maitra, a disease specialist at the University of Texas MD Anderson Cancer Center, who was not involved in the study. “By that standard, it’s a milestone.”

The study was small: Only 16 patients, all Caucasian, received the vaccine, part of a treatment regimen that also included chemotherapy and a drug designed to prevent tumors from evading people’s immune responses. And the study couldn’t completely rule out factors other than the vaccine contributing to better outcomes in some patients.

“It’s relatively early days,” says Dr. Patrick Ott of the Dana-Farber Cancer Institute.

Beyond that, “cost is a major barrier to wider use of these types of vaccines,” says Dr. Neeha Zaidi, pancreatic cancer specialist at Johns Hopkins University School of Medicine. That could potentially cause inequalities in access.

But the simple fact that scientists were able to create, quality-check and deliver personalized cancer vaccines so quickly — patients started getting the vaccines intravenously about nine weeks after their tumors were removed — was a promising sign, experts said.

Since the study began in December 2019, BioNTech has shortened the process to less than six weeks, said Dr. Ugur Sahin, a co-founder of the company, who worked on the study. Ultimately, the company wants to be able to make cancer vaccines in four weeks.

And since it first started testing the vaccines about a decade ago, BioNTech has cut costs from about $350,000 per dose to less than $100,000 by automating parts of production, said Dr. Sahin.

A personalized mRNA cancer vaccine developed by Moderna and Merck reduced the risk of relapse in patients undergoing surgery for melanoma, a type of skin cancer, the companies announced last month. But the latest study raised the bar by targeting pancreatic cancer, which is thought to have fewer genetic changes that would make it ripe for vaccine treatments.

In patients who did not appear to respond to the vaccine, the cancer returned about 13 months after surgery. However, patients who did respond showed no signs of relapse during the approximately 18 months they were followed.

Intriguingly, one patient showed signs of a vaccine-triggered immune response in the liver after an unusual growth developed there. The growth later disappeared in imaging tests.

“It’s anecdotal, but it’s nice confirmatory data that the vaccine can get into these other tumor regions,” said Dr. Nina Bhardwaj, who studies cancer vaccines at the Icahn School of Medicine at Mount Sinai.

Scientists have struggled for decades to create cancer vaccines, in part because they trained the immune system on proteins found on both tumors and normal cells.

However, tailoring vaccines to mutated proteins found only on cancer cells may have helped elicit stronger immune responses and open new avenues for treating each cancer patient, said Ira Mellman, vice president of cancer immunology at Genentech, who together developed the pancreatic cancer vaccine with BioNTech.

“Just establishing the proof of concept that vaccines can actually do something in cancer after, I don’t know, 30 years of failure probably isn’t a bad thing,” said Dr. Mellman. “We’ll start with that.”