Messenger RNA, or mRNA, which had generated excitement in the cancer research community long before it became popularly associated with the Covid vaccine, is now offering glimmers of hope, with a number of successes in early-stage trials involving patients with pancreatic cancer. The key development, writes MedicalBrief, comes on the heels of other encouraging news about an experimental drug for pancreatic cancer.
Scientists are optimistic after a small group of cancer patients has shown strong immune response to an mRNA-based vaccine, which has been years in the making.
One of them is librarian Vita Sara Blechner, whose life changed six years ago. She was at home in New York when she felt shooting pains in her back. After an acid reflux pill didn’t help, her husband suggested a trip to the emergency room.
It was 7 March 2020. Doctors put Blechner, then 67, through a sonogram and a CT scan. The results shocked her.
“They said I have a tumour on my pancreas. I said: ‘This can’t be happening to me. I don’t drink or smoke. I’m leading a healthy life’.”
After two anxious days in the hospital, Blechner headed home and weighed her options. There weren’t many. Pancreatic cancer is notoriously unforgiving: just one in four patients lives a year after their diagnosis. One in 10 makes it two years.
Blechner, 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.
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 excitement in the cancer research community.
BioNTech, which 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 Centre at Johns Hopkins University. “There have 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, said the recent stretch of positive real-world results helped drive the announcement by the National Cancer Institute that it would help raise $200m specifically for novel cancer vaccines.
“We’re getting lots of support from NCI for 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 Centre, including Dr Vinod Balachandran, director of MSK’s Olayan Centre 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 said. “That’s because our body’s immune systems are hard-wired to recognise 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 – derived from our own tissues.”
Much of Balachandran’s work in the past two decades has focused on pancreatic tumours 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 believed 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% of pancreatic cancer patients who live more than five years from diagnosis. He found their immune systems were especially good at spontaneously recognising cancer cells as foreign.
In fact, Balachandran said, these patients had about 12 times as many T-cells inside their tumours as average patients. The same T cells were circulating for more than a decade, in some cases.
Balachandran also realised these weren’t generic cancer-fighters. “These T cells were recognising mutations,” he said, “but each person’s immune system was recognising their cancer as foreign in a very specific way. To replicate this would require us to teach each person’s immune system how to recognise their individual cancer. It would be an individualised vaccine. And the best technology for rapid custom cancer vaccination was to use RNA.”
Research volunteer
After Blechner signed on for the trial, the first step was surgery. She underwent a Whipple procedure to remove the tumour in the head of her pancreas. In a lab at MSK, the tumour was preserved and sliced into fine pieces, each thinner than a human hair.
Within 72 hours, the package was en-route to Germany, where BioNTech technicians started processing the material into a clear liquid: a personalised vaccine, custom-made for her.
A little more than two months after her diagnosis, the vaccine concoction from Germany arrived back in New York. By then, she had received 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, she would lie in a hospital bed for eight hours while the vaccine coursed through her body.
After nine weeks, she was ready for the next step: chemotherapy. But chemo was a fiasco. Blechner suffered with side effects so severe that doctors had to halt treatment.
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: she not only survived longer than anyone expected, she’s still doing well and showing no sign of cancer.
And she’s no 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 presented last week at the American Association of Cancer Research meeting in San Diego.
Said Balachandran: “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 multi-site trial has been under way for a year.
The announcement comes on the heels of other encouraging news for pancreatic cancer patients.
Earlier this month, a former US Senator, Ben Sasse, who has been battling advanced pancreatic cancer, said he had been taking an experimental drug that caused his tumours to shrink, albeit with some painful side effects.
Last week, Revolution Medicines, the California-based biotech company running the phase 3 trial of which Sasse is part, 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.
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.
The low point came in May, when the White House proposed an unprecedented cut of more than 40% to funding for the National Cancer Institute.
Twenty-six days later, in an apparently unrelated move, the US Department of Health and Human Services cancelled a $590m 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 cancelled its review of Moderna’s mRNA-based flu vaccine, while criticising 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 more than $50bn. They can fund their own research,” Makary said in February.
Still, many researchers who once saw a bright future felt their faith shaken.
Dr Ryan Sullivan, Director of the Centre for Melanoma at Mass General Brigham Cancer Institute, said mistrust of mRNA vaccines since the pandemic has made it harder to recruit people into his clinical trials.
One technology, many paths
Sullivan is an investigator on multiple studies with mRNA vaccines, including a large-scale trial run by 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% over five years. A larger phase 3 trial is under way, 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 personalised, meaning an individual patient’s tumor cells are used to engineer a highly specific immune response.
Another approach involves generalised 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 tumour type in hopes of stimulating the immune system into a more aggressive response.
Dr Elias Sayour, a paediatric 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 generalised vaccine, using mRNA to stimulate production of a protein called PD-L1, making their tumours more susceptible to immunotherapy.
It worked.
“We’ve discovered that mRNA doesn’t need to be specific, to reprogramme the immune response,” he said.
“We’re trying to create a new paradigm. It takes weeks to create a personalised vaccine. The idea of universalisation is to wake up the immune system faster.”
He said 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 personalised 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 Centre. They reviewed records of more 1 000 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 got 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 been given 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 mRNA also acts as a siren call to the overall immune system.”
Grippin is now collaborating with Sayour to plan a trial where patients will be intentionally given a Covid vaccine before starting cancer treatment.
Money flowing but still tight
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 on 17 March 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 tumour – was approved by the NCI last year. But after the agency almost halved its total number of awards, he said the money never arrived.
He expects the work to go forward, eventually, but it will take time to find the funding. “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, thanks to the Covid experience, mRNA vaccines have a particularly extensive record.
“We’ve seen two-billion-plus injections, and there are no data to show that mRNA vaccines cause any serious problems,” Jaffee said.
See more from MedicalBrief archives:
mRNA vaccine shows promise in pancreatic cancer trial
Small pancreatic cancer vaccine trial shows promise
mRNA vaccine can recognise neoantigens in pancreatic cancers – US study