Personalized mRNA Vaccines Will Revolutionize Cancer Treatment—If Federal Funding Cuts Don’t Doom ThemNEWS | 21 November 2025As soon as Barbara Brigham’s cancerous pancreatic tumor was removed from her body in the fall of 2020, the buzz of a pager summoned a researcher to the pathology department in Memorial Sloan Kettering’s main hospital in New York City, one floor below. Brigham, now 79, was recovering there until she felt well enough to go home to Shelter Island, near the eastern tip of Long Island. Her tumor and parts of her pancreas, meanwhile, were sent on an elaborate 24-hour course through the laboratory. Hospital staff assigned the organ sample a number and a unique bar code, then extracted a nickel-size piece of tissue to be frozen at –80 degrees Celsius. They soaked it in formalin to prevent degradation, then set it in a machine that gradually replaced the water in each cell with alcohol.
Next, lab staff pinned the pancreas to a foam block, took high-resolution images with a camera fixed overhead and used a scalpel to remove a series of sections of tumor tissue. These sections were embedded in hot paraffin and cut into slices a fraction of the thickness of a human hair, which were prepped, stained and mounted on glass slides to be photographed again. By the time a pathologist looked at Brigham’s tumor under a microscope the next day, more than 50 people had helped steer it through the lab. Still, this work was all a prelude.
The real action came some two months later, when Brigham returned to the hospital to receive a vaccine tailored to the mutations that differentiated her tumor from the rest of her pancreas. Made of messenger RNA (mRNA) suspended in tiny fat particles, the vaccine was essentially a set of genetic instructions to help Brigham’s immune system go after the mutant proteins unique to her tumor cells. It was, in other words, her very own shot.
On supporting science journalism
If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.
It’s been four years since Brigham received the last of nine doses of her personalized vaccine. In that time she’s seen one grandchild finish college and get married and another embark on a Ph.D. She has attended dozens of high school basketball and volleyball games for her third and fourth grandchildren and cradled the family’s newest arrival, a granddaughter born last year. She hosts a weekly mah-jongg-and-dessert gathering for a group of friends on Shelter Island and tries to live out her mother’s maxim of having “a little adventure” each and every day. “I’m a little crippled here and there with arthritis,” Brigham says, but “I never sit still.” And she remains free of pancreatic cancer.
Brigham’s recovery came as part of a small phase 1 clinical trial conducted by Memorial Sloan Kettering in partnership with pharmaceutical companies Genentech and BioNTech—the latter, along with Pfizer, helped to produce the first approved mRNA vaccine for COVID-19. Brigham was one of 16 patients in the study who received the vaccine, administered in tandem with standard drugs, and one of eight who experienced a significant immune response. Six of those eight patients are still in remission, along with one of the eight others who did not show much immune response to the vaccine.
Seven of 16 might not sound like much. But that number suggests that the vaccine has tantalizing potential. Pancreatic cancer can be exceptionally fast-growing, and its first signs—weight loss, cramping, a touch of jaundice—are easily missed, so by the time it is diagnosed it is almost always lethal. Only 8 percent of patients with the most common form of the cancer, ductal adenocarcinoma, survive to the five-year mark, and the vast majority of people with the disease show little response to treatment.
The results of Brigham’s trial were also an early sign that mRNA vaccines may be effective for a wide variety of cancers: whereas pancreatic cancer is known for its low rate of mutations, the earliest data on personalized mRNA vaccines came from studies of melanoma, which researchers had targeted specifically because it tends to mutate so frequently. An earlier phase 2 trial in patients with advanced melanoma found that for those who received both a personalized mRNA vaccine and so-called immune checkpoint inhibitors, the risk of death or recurrence decreased by almost half compared with those who got only checkpoint inhibitors. Ongoing companion trials are targeting kidney and bladder carcinomas and lung cancer. In each case, the vaccine is additive: administered after surgery and with standard drugs. The shot’s job is to prime the immune system to recognize abnormal proteins arising from mutations and attack any lingering malignancy that escaped conventional treatments—or stamp out future recurrence.
Seeing promising results in fundamentally different kinds of tumors has motivated researchers to pursue personalized mRNA vaccines much more broadly. In doing so, they’ve developed an approach at the nexus of several important trends, pairing insights about our immune system’s response to cancer with advances in vaccine production spurred by the COVID pandemic, the rise of algorithms powered by artificial intelligence, and the plummeting cost of genetic sequencing. Today there are at least 50 active clinical trials in the U.S., Europe and Asia targeting more than 20 types of cancer. A melanoma trial led by pharmaceutical companies Moderna and Merck has now reached phase 3, the last step before a medicine can be approved for public consumption. Personalized melanoma vaccines could be available as early as 2028, with mRNA vaccines for other cancers to follow.
But the promise of this novel approach couldn’t have come at a more perilous time for the field. In the first weeks of the second Trump administration, U.S. cancer research was thrown into unprecedented turmoil as federal grants were terminated en masse. According to one Senate analysis, funding from the National Cancer Institute was cut by 31 percent in just the first three months of 2025.
By March cancer researchers worried that mRNA vaccines were facing particular scrutiny. KFF Health News reported that Michael Memoli, acting director of the National Institutes of Health, had asked that any grants, contracts or collaborations involving mRNA be flagged for Health and Human Services Secretary Robert F. Kennedy, Jr., best known prior to assuming that role as one of the nation’s most prominent anti-vaccine campaigners. Suddenly, the optimism around personalized mRNA vaccines was overshadowed by a sense that the public investment that sustained cancer research was being dismantled piece by piece.
Much of cancer’s biological power comes from the fact that to the body, it doesn’t always seem like a pathogen. Because cancer arises from mutations in each patient’s own DNA, the disease complicates our immune system’s central task of differentiating between body and foreign object, host and invader, “self” and “not self.”
Physicians long hypothesized that there was a link between cancer and swelling—a critical sign that the immune system “sees” an enemy to ward off. In the 1890s William Coley, now known as the father of immunotherapy, successfully spurred remission in patients with inoperable tumors by injecting them with bacteria like those that cause strep throat. But the mechanisms behind Coley’s treatments were poorly understood, and for decades after his discovery, researchers weren’t sure our immune systems could detect cancer at all.
Because doctors didn’t know exactly how the body perceives and responds to cancer, early treatments were highly invasive and highly toxic: The first tactic was major surgery on the organs where cancer was taking root. That was followed in the 20th century by the development of systemic radiation and chemotherapy to attack cancer cells throughout the body. Over time oncologists narrowed and refined these approaches incrementally, using more precise surgery, more focused radiation and chemo that killed fewer normal cells as collateral. Still, the dream was to harness immunotherapy, which represented a dramatic departure from the usual tactics in seeking to use the human body’s own systems to go after cancer in a more targeted way.
As demand for COVID vaccines has slackened, there has been a rush to apply mRNA technology to a long list of illnesses.
The first real proof that immune cells are capable of recognizing tumors didn’t come until the 1950s and 1960s. Gradually, researchers came to understand that cancer deploys a host of tricks to suppress the immune response to growing tumors. Some forms of cancer use fibrous tissue called stroma to construct shields that make it difficult for immune cells to penetrate or attack tumors. Other cancers take advantage of the balancing act our immune systems are always performing when they decide how heavily to invest the body’s defenses in warding off a given threat. Some tumors produce proteins that can shut down key immune cells. Tumors may even recruit immune cells to promote the growth of blood vessels that will supply them with oxygen and nutrients.
As scientists learned more about how cancer manipulates the immune system, they started identifying ways to thwart it. Inside our cells, proteins are constantly being chopped up into smaller sequences of amino acids, some of which are then presented on the cell surface as part of what’s collectively known as the major histocompatibility complex, or MHC—essentially the immune system’s tool for differentiating self and foreign molecules. When the immune system detects a protein from a pathogen, it’s supposed to dispatch killer T cells to eliminate the invader. Some cancers can interfere with this process by hijacking the checkpoint proteins that keep our immune system from revving out of control and using them to turn T cells off. Starting in the mid-1990s, several research teams found success by treating mice with checkpoint inhibitors, then a new class of drugs designed to keep tumor cells from concealing their identity and signaling, effectively, “nothing to see here.” Thirty years on, checkpoint inhibitors have become a transformative tool in cancer treatment, especially for melanoma.
The research that went into developing checkpoint inhibitors showed conclusively that immune cells detect cancer much in the same way they identify other pathogens: through differences in protein structure determined by DNA—a crucial insight. But as revolutionary as checkpoint inhibitors have been for immunotherapy, they don’t work for everyone—far from it. Some 80 percent of patients do not respond to this class of drugs. Researchers are still trying to understand all the mechanisms that play a role in determining who does respond, but one key factor is whether the immune system is able to recognize tumor cells on the basis of their mutations.
This is where mRNA vaccines come in. Jason Luke, a melanoma researcher who now serves as chief medical officer of mRNA-medicine start-up Strand Therapeutics, helped to design several ongoing clinical trials of mRNA vaccines for cancer. He explains that both checkpoint inhibitors and mRNA vaccines build on our deep evolutionary adaptation for fighting pathogens by identifying the proteins they shed in our bodies. But checkpoint inhibitors are effective only if the patient’s immune system recognizes the cancer as a threat. In contrast, mRNA vaccines have the potential to work even in patients whose cancers haven’t spurred much immune response. The trick, Luke says, is using computational tools to decipher which of a given tumor’s mutations are most likely to be found by the immune system.
On a Monday morning last April, I visited surgical oncologist Vinod Balachandran at his lab on the eighth floor of the Memorial Sloan Kettering Cancer Center. Balachandran led the trial Brigham participated in, and he now is director of a center for cancer vaccines that the institution launched in 2024. The entrance to his lab is at the end of a hallway lined with big freezers holding tissue samples.
When I arrived, Balachandran met me just beyond a pair of swinging doors, where postdocs hunched over laptops under rows of high shelves packed with boxes of pipettes and assay plates. He strode to the window and pointed to the brick façade of the main hospital across the street, explaining that tissue samples taken after surgery have only a short distance to travel to the lab, sometimes through a tunnel under East 68th Street. “The proximity of the laboratory tower to where patients are being treated is actually supercritical,” he says, because it allows the samples to be processed and put on ice quickly, minimizing the deterioration that begins as soon as tissue is removed from the body.
The work that culminated in Brigham’s vaccine grew out of research into a subset of pancreatic cancer survivors known as exceptional responders—the small percentage of people who make it to the five-year mark after a diagnosis. “These patients, you know, they’re very rare,” Balachandran says. Even at a facility as large as Memorial Sloan Kettering, which sees tens of thousands of cancer patients a year, it was possible to study this group with any precision only because of the hospital’s long-standing mandate to save samples of every patient’s tissue. When Balachandran joined the faculty in 2015, his research on long-term survivors relied on tissue samples taken more than a decade earlier.
In 2017 Balachandran and his collaborators published a study demonstrating that some patients with pancreatic ductal adenocarcinoma had more cells able to recognize the unique proteins that mutant tumor cells produced and that their immune systems seemed to develop a kind of long-term memory to fight recurrence. In some cases, immune cells with receptors that could bind to these cancer proteins persisted in the blood for more than a decade after the tumors that spawned them were removed. What if, Balachandran wondered, we could equip the 92 percent of patients who are not naturally exceptional responders with the same kinds of biological tools? “If you can teach the immune system to recognize the proteins in, say, pancreatic cancer, perhaps that could provide a blueprint,” he says.
As tumors grow and metastasize, they undergo a kind of compressed evolution in which normal cells with the host’s DNA accrue mutations that cause them to divide and multiply abnormally, forming an ever larger group of closely related tumor clones. Many mutations register in the form of abnormal proteins and protein fragments, called neoantigens, some of which accumulate on the surface of the proliferating tumor cells.
Balachandran compared this growing family tree of tumor clones with new variants in a group of viruses, like the Alpha, Delta and Omicron variants of SARS-CoV-2, which emerged as the COVID-19 pandemic wore on. “You’d want a COVID vaccine to be able to target each different virus in that rapidly evolving clade,” Balachandran says.
For the development of a cancer vaccine, mapping the evolutionary trajectory of a cancerous tumor is equally important, albeit with a different set of parameters. The goal is not to distinguish between the presentations of two related pathogens but rather to understand at what point a disease derived from one’s own body starts to register to the immune system as not self.
“At some point—we don’t think immediately—the immune system starts to notice,” says Benjamin Greenbaum, Balachandran’s colleague at Memorial Sloan Kettering’s Olayan Center for Cancer Vaccines, who led the computational work behind the vaccine given to Brigham. In later stages, tumors typically accumulate signs of immune system involvement even if the immune response hasn’t been effective—changes in the cell makeup of the microenvironment around the tumor, the display of checkpoint molecules. These signs can be understood as evolutionary adaptations on the part of the tumor in the race to evade detection, Greenbaum explains. “So then the question really became, Can we try to estimate what the immune system is really seeing in cancer?”
To develop a workable mRNA vaccine, Greenbaum and Balachandran had to both sequence the DNA of the cancerous tumors they were targeting and develop a framework for going after the right neoantigens—those abnormal proteins that offer clues to a tumor’s underlying mutations. Neoantigens are made up of short chains of amino acids from proteins with names that look like license plate numbers: PIK3CA, KDM5C. One overarching goal of their collaboration is to discern meaningful patterns in the frequency of the sequences across patients and across cancer types. What neoantigens survive one mutation after another? Which ones show up reliably under certain conditions or look most distinctive to the body’s immune defenses?
Some of these sequences, from so-called driver antigens, are present in most clones of a given tumor type. In pancreatic cancer, the driver mutation is often in a gene called KRAS, but the resulting antigens don’t seem to elicit a reliable immune response in long-term survivors. Instead, when Balachandran and his colleagues sequenced the blood of such survivors, the immune cells present in the highest concentrations were those adapted to antigens resulting from one-off, or “passenger,” mutations.
Another threat to personalized mRNA vaccines for cancer was coming into focus: mounting federal hostility to vaccines.
In 2017, at the time that the team published the results of the study, this was a counterintuitive finding. For decades researchers pursuing vaccines and other immune treatments for cancer had focused on melanoma because melanoma tumors have a high rate of genetic mutations. “It looks very different to the immune system than many other types of cancers do,” says Michael Postow, a medical oncologist at Memorial Sloan Kettering who is involved in clinical trials of mRNA vaccines for melanoma. “That made it a good target.” With all the mutant antigens it produces, melanoma should attract the immune system’s attention and trigger it to attack. The conventional wisdom about pancreatic cancer, in contrast, held that it produces so few mutations that it is unlikely to carry passenger antigens that could elicit an immune response.
With the results from the 2017 study of exceptional responders in hand, Balachandran was able to flip that argument on its head. Even if vaccines appear to be well suited for melanoma, there’s always a degree of uncertainty in selecting the right antigens to target. For starters, the sequencing of a pancreatic tumor biopsy like Brigham’s is really just a snapshot in time. Come back a few months or a few years later or wait for the patient to experience a recurrence, and there’s no guarantee the tumor clone that seemed dominant at the time of the initial sequencing will still be a factor in the disease. Each mutation can also have unpredictable effects, with the size, shape or biochemistry of the antigen in question shifting dramatically in response to the change of even a single amino acid.
What is more, not every antigen that corresponds to either self or not self is reliably expressed on the surface of the corresponding cell. A neoantigen that seems characteristic of the tumor might have a profile nearly identical to that of another self-antigen somewhere else in the body. In that case, a vaccine based on that neoantigen might fail to elicit much of an immune response, or it could provoke a response against the wrong target.
The study revealed a potential liability in a strategy for personalized mRNA vaccines that focused on melanoma: melanoma’s high rate of mutations gives rise to a large pool of plausible vaccine targets, but it presents just as many chances to guess wrong. A given tumor could have as many as 10,000 distinct proteins on the surface of its cells; you couldn’t possibly target every one. But in pancreatic cancer, Balachandran realized, the smaller number of mutations might improve the odds of picking a suitable antigen to target.
That insight underpinned the pitch Balachandran brought to Ugur Sahin, co-founder and CEO of German biotech company BioNTech. Their collaboration began before the COVID pandemic, but in 2020 BioNTech was consumed by the effort to bring the world’s first mRNA vaccine to market. Together with Moderna, the company demonstrated the vaccine’s safety through billions of doses administered worldwide with very few side effects.
Not only was mRNA safe for vaccine delivery, but, as Sahin knew from experience, it is also a flexible platform for genetic information. Whereas traditional vaccines typically require ongoing production of the exact virus they’re targeting, most of the genetic information in an mRNA vaccine can stay the same no matter which disease you’re fighting.
BioNTech’s COVID vaccine built on 30 years of work by Sahin and company co-founder Özlem Türeci that was originally intended for vaccines targeting cancer. As longtime collaborators who are also a married couple, they had tinkered with the nucleotide sequences on the molecule’s cap and tail that direct a vaccine to the right part of the cell and tell the immune system what to pay attention to, and they had improved the mRNA’s stability so that even a small dose of a vaccine could provoke a full-scale immune response. All that work could be incorporated into vaccines for other diseases; the only thing that needed to change was the genetic information in the middle of the molecule. After obtaining positive results for the mRNA vaccine for melanoma, Sahin agreed to partner with Balachandran to develop an mRNA vaccine for pancreatic cancer.
As global demand for COVID vaccines has slackened, there has been a mounting rush to apply mRNA technology to a long list of illnesses, including malaria, flu, tuberculosis and norovirus. Cancer is a natural target. Despite treatment advances, it remains broadly incurable and is a leading cause of death as life expectancies improve across the world. But because cancer vaccines must be personalized, the biggest change in approach to developing them for an mRNA platform comes not in development but in manufacturing. Both BioNTech and Moderna now confront something like the inverse of the challenge they faced in developing the first COVID shots.
Prior to the pandemic, both companies were upstarts among the giants of the pharmaceutical industry. Neither had brought a product to market. Moderna employed under 1,000 people and had manufactured fewer than 100,000 total doses of its clinical-stage vaccines. Once its SpikeVax received emergency use authorization from the U.S. Food and Drug Administration, the company quadrupled its workforce and produced more than a billion doses in just 18 months.
The task facing Scott Nickerson, who oversees Moderna’s manufacturing for individualized neoantigen therapies, was to reengineer a process perfected for producing mRNA vaccines for millions of people in batches of thousands of liters. For personalized vaccines, each batch would be a few milliliters at most and would have to be turned around in weeks.
To get there, Moderna is investing heavily in automation, partnering with a robotics firm to prepare sterile kits of raw materials for each batch and thereby minimize operator touch time on the manufacturing floor. The hope is that rather than following a single large batch of vaccine through the entire manufacturing process, workers will eventually be able to move from one small batch to the next after setup.
At both Moderna and BioNTech, the complex logistics of conducting the dozens of different quality-control tests required for each production run falls to algorithms powered by AI. Before being approved for release, doses of SpikeVax underwent 40 distinct tests that tracked the chemistry, biochemistry, microbiology and sterility of every vial. With COVID vaccines, the sterility test alone, which ensures that vials are not contaminated with organisms, took two weeks. Refinements have since compressed that test to eight days, Nickerson says. Ultimately the goal is to shrink it to five days and complete the other tests within that same window. “The reason it’s hard is we have to design the equipment,” he explains. “None of this stuff’s off-the-shelf.”
At the same time, the background science is, at least in theory, easily adapted from work that’s already been done. Lennard Lee, an adviser to the U.K.’s National Health Service overseeing the rollout of clinical trials for cancer vaccines, says the pandemic gave regulators there a running start on trials for mRNA cancer vaccines. In partnership with BioNTech, the NHS launched a program that aims to provide personalized vaccines to up to 10,000 cancer patients in the next five years. And the NHS and Moderna have invested in a facility that could produce up to 250 million vaccines per year.
In that interval, as manufacturers work to reduce production times and costs, clinical trials will evaluate alternative dosage and delivery mechanisms, Lee says. Although current protocol is for vaccines to target micrometastases—small groups of cancer cells that spread to other parts of the body and linger after cancerous tumors are removed surgically—there’s no shortage of adjustments that might follow from more data or improved screening. Could one deliver a therapeutic vaccine to tackle a tumor before it is large enough to operate on? Or maybe one could even administer a prophylactic shot that prevents tumor formation in the first place?
With a unified health system and world-class research and manufacturing facilities, Lee says, the U.K. is well positioned to advance research that would answer such questions. Fully realizing the potential of personalized mRNA vaccines for cancer, however, will require more trials in the U.S., which has many more cancer research centers than the U.K. But the ability of the U.S. to lead this effort is now in jeopardy.
The federal government has long been the dominant source of funding for cancer research in the U.S. Miriam Merad, a cancer immunologist at the Icahn School of Medicine at Mount Sinai in New York City, says that in a typical year, funding from the NIH accounts for more than half of the research budget at her institution.
In President Donald Trump’s first term, threatened cuts to the NIH never quite materialized. Society is not going to let that happen, Merad thought. But just weeks into Trump’s second term, the NIH announced plans to limit indirect contributions to research grants to 15 percent, meaning that for every $100 in funding awarded, only $15 extra would be included for overhead—a dramatic departure from historical rates in the range of 50 to 60 percent.
“This is an operation,” Merad says, gesturing to the building where she works, which is dotted with six-figure pieces of equipment and has an entire floor dedicated to rearing mice used in research. “We have to pay salaries; we have to buy food for the animals. We have to pay service contracts because we have instruments that need to be serviced all the time.” These are not expenses that can be easily paused or restarted based on the fate of a single grant. Within just a few months of the NIH announcement, Merad’s department had reduced hires of new postdocs, and Mount Sinai’s medical school had to shrink the size of its incoming class.
By May another threat to personalized mRNA vaccines for cancer was coming into focus: mounting federal hostility to vaccines. Senate Republicans convened a hearing entitled “The Corruption of Science and Federal Health Agencies,” featuring the false claim that as many as three out of four deaths from COVID were caused by mRNA vaccines deployed to stop the pandemic. (In fact, COVID vaccinations saved an estimated 2.5 million lives between 2020 and 2024, according to a study published earlier this year.) In June, Kennedy fired all 17 members of the Advisory Committee on Immunization Practices, which makes recommendations on federal vaccine policy. He eventually replaced them with his own advisory committee, which includes several anti-vaccine stalwarts. Kennedy has also slashed research funding for mRNA vaccines. In August he canceled nearly $500 million supporting the development of mRNA vaccines against viruses such as SARS-CoV-2 and influenza. The move intensified the fears of researchers who want to develop mRNA vaccines for other illnesses, among them cancer.
After my visit to Memorial Sloan Kettering, Balachandran’s team shared a chart that plotted Brigham’s immune response to her personalized mRNA vaccine. Along the bottom, triangles marked the dates of her surgery and each of the nine doses of the vaccine she received over the course of a year. Above them a cluster of brightly colored lines showed the share of her body’s T cells targeting the specific mutant proteins in her cancerous tumor. At first, when Brigham’s tumor was removed, cells trained to go after each cancer clone were somewhere on the order of one in 500,000 T cells in her blood. A few months after surgery, when she’d had four doses of the vaccine, the lines shot up almost vertically, showing that the most common cancer fighter at that point accounted for around one in 20 to one in 50 T cells—an increase of more than 20,000-fold.
Those T cells dipped a bit in the months before Brigham’s last booster shot, given almost a year after her tumor was removed. But they remained in the same range even three years on. A phase 2 clinical trial evaluating the safety and efficacy of the vaccine in a larger patient group is currently underway.
The vaccine for Brigham’s cancer was just nine tiny vials of liquid administered through an IV, a private message that only her immune system was meant to decode. But the effort that delivered that coded message was a deeply collective enterprise, one that stretches back through the hundreds of thousands of tissue samples collected, stored and analyzed at Memorial Sloan Kettering, each one taken from the body of a patient who might not have survived their cancer. Also in that vaccine were the contributions of generations of taxpayers who never got to see these results. Perhaps their descendants will be able to beat the disease—if society continues to support this vital work.Author: Kate Wong. Rowan Moore Gerety. Source
