After a year of turmoil, cancer researchers see promising signs for mRNA vaccines

MRNA is known to most people from high school science classes or for its use in Covid-19 vaccines. (Daniel Leal/AFP/Getty Images via CNN Newsource)

Vita Sara Blechner’s life changed on a Saturday afternoon. The middle school librarian was home in Oceanside, New York, when she felt shooting pains in her back. After an acid reflux pill couldn’t soothe the fiery feeling, her husband suggested a trip to the emergency room.

It was March 7, 2020, just days before Covid-19 would turn New York City’s hospitals into something approaching a war zone. If the doctors knew what was coming, they didn’t let on. They were cool and collected as they put Blechner, then 67, through a sonogram and a CT scan. But the pictures turned her world upside-down.

“They said I have a tumor on my pancreas. And I said, ‘No, it can’t be. This can’t be happening to me. I don’t drink. I don’t smoke. I’m leading a healthy life.’”

After an anxious two days in the hospital, Blechner headed home and weighed her options. There weren’t many. Pancreatic cancer is notoriously unforgiving: Just 1 in 4 patients lives a year after their diagnosis. Just 1 in 10 makes it two years.

Blechner felt the numbers in the pit of her stomach as she, her husband and their three adult sons made calls and pored over the internet, deciding her next move. They settled on a path that would land Blechner in a fast-moving and often misunderstood realm of cancer research.

Messenger RNA, or mRNA, is a single-stranded molecule that delivers genetic information from DNA to direct the formation of proteins. It’s known to most people from high school science classes or for its use in Covid vaccines. But long before anyone had heard of Covid, mRNA was generating intense excitement in the cancer research community. BioNTech, the German company that designed the Covid vaccine for Pfizer, adapted that vaccine from a platform it had been using to develop cancer treatments for nearly a decade.

The mRNA-based Covid vaccines produced by Pfizer and Moderna helped blunt the impact of the pandemic but also sparked political backlash that, in the past year, has threatened to slow or derail dozens of potential cancer treatments. Now, after a tumultuous 12 months, there are signs that the mRNA train is still on track.

“It’s exciting,” said Elizabeth Jaffee, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. “There’s been a number of successes in early-stage, positive trials.”

Dr. Catherine Wu, a professor of medicine at Dana Farber Cancer Institute and Harvard Medical School, says the recent stretch of positive real-world results helped drive the recent announcement by the National Cancer Institute that it would help raise US$200 million specifically for novel cancer vaccines.

“We’re getting a lot of support from NCI in terms of developing and promoting cancer vaccines, and mRNA vaccines are a major part of that portfolio,” she said.

An unforgiving enemy

To guide her treatment, Blechner turned to doctors at Memorial Sloan Kettering Cancer Center, including Dr. Vinod Balachandran, director of MSK’s Olayan Center for Cancer Vaccines.

It’s more challenging to make a vaccine against cancer than it is to create a vaccine against a virus or bacteria, Balachandran says. “That’s because our body’s immune systems are hard-wired to recognize viruses and pathogens as foreign, so a vaccine is teaching our body to do something it already wants to do. In contrast, cancer is ourselves. It’s derived from our own tissues.”

Much of Balachandran’s work the past two decades has focused on pancreatic tumors because the disease is such a tough nut to crack. “It’s a cancer where nothing had really worked,” he said.

When Blechner arrived at MSK, he was just launching a trial of an experimental mRNA-based vaccine against pancreatic cancer, in combination with standard immunotherapy and chemotherapy. He felt like a successful vaccine would also have the potential for wider application. “If we could break through and crack the toughest one, it could unlock how to crack the other [types of cancer], because it would provide a blueprint.”

To develop the vaccine, he began by studying “super-survivors”: the fewer than 10 per cent of pancreatic cancer patients who live more than five years from the time of diagnosis. He found that their immune systems were especially good at spontaneously recognizing cancer cells as foreign. In fact, Balachandran says, these patients had about 12 times as many T-cells - a specialized type of immune cell - inside their tumors as average patients. The same T cells were circulating for more than a decade, in some cases.

Balachandran also realized that these weren’t generic cancer-fighters. “These T cells were recognizing mutations,” he said, “but each person’s immune system was recognizing their cancer as foreign in a very specific way. To replicate this would require us to teach each individual person’s immune system how to recognize their individual cancer. It would be an individualized vaccine. And we felt the best technology for rapid custom cancer vaccination was to use RNA.”

Taking a chance as a research volunteer

After Blechner signed on for the trial, the first step was surgery. She underwent what’s known as a Whipple procedure to remove the tumor in the head of her pancreas. In a lab at MSK, the tumor was preserved and sliced into fine pieces, each thinner than a human hair. In less than 72 hours, the package was en route to Germany, where technicians at BioNTech took steps to process the material into a clear liquid: a personalized vaccine, custom-made for Vita Sara Blechner.

A little more than two months after her diagnosis, the vaccine concoction from Germany arrived back in New York. By that time, she had been given a dose of an immune checkpoint inhibitor, an immunotherapy drug designed to make her immune cells more effective in fighting cancer. For weekly infusions of the vaccine, her husband, Simon, would drive Blechner from Oceanside to the MSK hospital on Manhattan’s East Side. It was the height of the Covid pandemic, so instead of running errands or visiting friends after dropping her off, he would drive through empty streets and wait back home on Long Island. Blechner would lie in a hospital bed for eight hours while the vaccine coursed through her body, until Simon returned to pick her up.

After nine weeks, she was done and ready for the next step in her treatment: chemotherapy. But chemo was a fiasco. Blechner suffered mightily, with side effects so severe that doctors had to halt treatment. “I got very sick,” she recalled.

“I only had three sessions before they had to stop, and I was in and out of the hospital three or four times. I was down to 90 pounds. I had no appetite. I was constantly nauseous, and my liver was damaged,” she said. “My doctor said to me she never thought she’d see me again.”

By the time she felt strong enough to try again, her doctors felt it would be unsafe to resume. She hoped that stopping early wouldn’t make a difference. But she would have to wait and see.

She tells this story more than six years later: Blechner not only survived longer than anyone expected, she’s still doing well and showing no sign of cancer.

And she’s no singular exception. Of 16 patients in Balachandran’s trial, eight showed a dramatic immune response to the mRNA-based vaccine. Seven of the eight are alive and well six years after the trial began, a finding that was to be presented Monday at the American Association of Cancer Research meeting in San Diego.

“It’s exciting,” Balachandran said. “The implication is that you can make a very strong immune response against the toughest of cancers, and it can last for this long. So if you could do it here, you could potentially do it in many other cancers.”

Although a study with 16 patients is far from definitive, a larger multisite trial has been underway for a year.

The announcement comes on the heels of other encouraging news for pancreatic cancer patients. Earlier this month, the New York Times published an interview with former US Sen. Ben Sasse of Nebraska, who has been battling advanced pancreatic cancer and told the Times he’s been taking an experimental drug that caused his tumors to shrink, albeit with some painful side effects. Last week, Revolution Medicines, the California-based biotech company running the phase 3 trial that Sasse is part of, said in a news release that for patients whose cancer had spread, the drug nearly doubled survival time to 13.2 months, compared with 6.7 months among participants who didn’t get the drug. Revolution also said it will seek approval from the US Food and Drug Administration for the drug, called daraxonrasib.

A promising technology under fire

Although much smaller than the Revolution study, the MSK trial stands as proof of concept for the promise of mRNA-based vaccines. The field has been a source of great excitement in recent years. But it also faced backlash in the wake of the pandemic and public concerns over Covid vaccines, even as most experts say major safety concerns around the latter are unfounded.

For cancer researchers, an early warning sign appeared in March 2025, when scientists reported that the acting director of the National Institutes of Health, Dr. Matthew Memoli, had sent a letter asking that all grants, collaborations or contracts involving mRNA be flagged.

For some, the low point came in May, when the White House proposed an unprecedented cut of more than 40 per cent to funding for the National Cancer Institute. Twenty-six days later, in an apparently unrelated move, the US Department of Health and Human Services canceled a $590 million deal with Moderna to develop an mRNA-based vaccine against emerging pandemic influenza. In August, HHS followed up by announcing it would no longer fund mRNA research through the Biomedical Advanced Research and Development Authority. The latter move involved the cancellation of 22 separate contracts.

More recently, the FDA canceled its review of Moderna’s mRNA-based flu vaccine, while criticizing the design of the company’s clinical trial, but the agency reversed its decision a week later after fierce criticism.

FDA Commissioner Dr. Marty Makary has said the agency bears no animus toward mRNA and that it terminated contracts last year solely to save taxpayer money. “The companies that made mRNA vaccines made over $50 billion. They can fund their own research,” Makary said at a news conference in February.

Still, many researchers who once saw a bright future felt their faith shaken. “The external threats are real,” Wu said. “It forced us to really step back and think. I wouldn’t be genuine if I said we weren’t all concerned.”

Dr. Ryan Sullivan, director of the Center for Melanoma at Mass General Brigham Cancer Institute, says mistrust of mRNA vaccines since the pandemic has at times made it harder to recruit people into his clinical trials.

“Most people don’t have significant concerns, but some are reluctant,” Sullivan said. “The skepticism over vaccines in general is a little bit lessened around cancer vaccines, but not totally, and some people are resistant to the concept, even when they’re fighting cancer.”

One technology, many paths

Sullivan is an investigator on multiple studies with mRNA vaccines, including a large-scale trial run by drugmakers Moderna and Merck, testing an mRNA-based therapy in combination with Keytruda, an immunotherapy drug, as a treatment for melanoma. In January, the companies announced that the combination cut the death rate for participants in their study by 49 per cent over five years. A larger phase 3 trial is underway, and the companies are also testing the therapy against non-small cell lung cancer, bladder cancer and renal cell carcinoma.

Like the vaccine that helped Blechner, Merck and Moderna’s melanoma treatment is personalized, meaning an individual patient’s tumor cells are used to engineer a highly specific immune response. Another approach involves what are called generalized or off-the-shelf vaccines, that are not tailored to each individual patient. BioNTech and the Moderna/Merck collaboration are both working on approaches that use mRNA to encode and deliver a predefined set of antigens - immune targets - that are typically shared across patients with a given tumor type in hopes of stimulating the immune system into a more aggressive response.

Dr. Elias Sayour, a pediatric oncologist and researcher at the University of Florida, has gone a step further in the “generic” direction, testing mRNA vaccines that don’t code for any specific antigen at all. In a study published last year in the journal Nature Biomedical Engineering, Sayour treated mice with a generalized vaccine, using mRNA to stimulate production of a protein called PD-L1, making their tumors more susceptible to immunotherapy. It worked.

“We’ve discovered that mRNA doesn’t need to be specific, to reprogram the immune response,” Sayour said.

“We’re trying to create a new paradigm,” he added. “It takes weeks to create a personalized vaccine. The idea of universalization is to wake up the immune system more rapidly.”

He says the two approaches could, in theory, complement each other: A newly diagnosed patient might receive an off-the-shelf vaccine to ramp up their immune system and a personalized vaccine later in their course of treatment.

A recent illustration of the “universal vaccine” approach came in a study led by Drs. Adam Grippin and Steven Lin of MD Anderson Cancer Center. They reviewed records of more than a thousand cancer patients treated with immune checkpoint inhibitors and found that getting an mRNA-based Covid vaccine was linked to a significantly better response to cancer drugs.

Patients with small cell lung cancer who had gotten a Covid shot within 100 days of starting treatment lived nearly twice as long as those who hadn’t. For those with melanoma, researchers couldn’t calculate the difference in survival time because so many of the patients who had gotten a Covid vaccine were still alive.

“Most people think about vaccines as a laser-guided missile,” said Grippin, who before coming to MD Anderson was a graduate student in Sayour’s lab. “That may be true, but our research suggests that mRNA also acts as a siren call to the overall immune system.”

Grippin is now collaborating with Sayour to plan a trial in which patients will be intentionally given a Covid vaccine prior to starting cancer treatment.

Money flowing but still tight

Dr. Robert Vonderheide, director of the Abramson Cancer Center at the University of Pennsylvania and president-elect of the American Association for Cancer Research, says that the field took hits last year but that public pressure turned the tide. “The entire country has been asking, ‘How valuable is cancer research to our society?’ And what we heard from the public and our patients is, it’s super-important.”

Federal research grants have started to flow again, after major interruptions over the past several months. Last week, NCI Director Anthony Letai told the Cancer Letter podcast that 22 competitive grants were awarded March 17 and another 167 awarded over the next three-plus weeks.

Still, there are scars. One of Sayour’s proposals – to test an mRNA-based vaccine against a rare form of childhood brain tumor – was approved by the NCI last year. But after the agency reduced by nearly half its total number of awards, he says the money never arrived.

He says he expects the work to go forward, eventually, but it will take time to find the funding. “As you can imagine, I’ve shifted my approach to finances,” Sayour said. “The reality is, there’s a lot of dependency on the federal government, and if you put all your faith in one stock, you could go under pretty quickly.”

While federal funding remains tight, the most prominent mRNA cancer vaccines have attracted industry support and are not reliant on grants. Moderna says it expects to release data from the phase 3 melanoma trial this year. Genentech and BioNTech are sponsoring the global multisite test of the vaccine that Blechner received, with Balachandran leading efforts at MSK.

“You need a platform that is fast and potent, flexible and scalable,” Balachandran said. “There are other ways to generate immune responses, but the RNA platform at the moment seems to be superior.”

Although none of the cancer vaccine platforms has inspired major safety concerns, Jaffee notes that thanks to the Covid experience, mRNA vaccines have a particularly extensive record. “We’ve seen two-billion-plus injections, and there’s no data to show that mRNA vaccines cause any serious problems,” she said.

Vita Sara Blechner is no longer waiting for the other shoe to drop. “I guess once I hit my fifth year [cancer-free], it really sank in that I’m doing well. I said, ‘I beat the odds.’ Now I’m grateful every day,” she said. “I’m really looking forward to my sons getting married. I’m looking forward to the holidays, since I have the strength to do the work and have everyone over. We just had a family event a week ago, and we danced and ate and had a great time. Every day is wonderful.”

Caleb Hellerman, CNN