An experimental mRNA vaccine boosted the tumor-fighting effects of immunotherapy in a mouse-model study, bringing researchers one step closer to their goal of developing a universal vaccine to “wake up” the immune system against cancer.
Published today in Nature Biomedical Engineering, the University of Florida study showed that like a one-two punch, pairing the test vaccine with common anticancer drugs called immune checkpoint inhibitors triggered a strong antitumor response.
A surprising element, researchers said, was that they achieved the promising results not by attacking a specific target protein expressed in the tumor, but by simply revving up the immune system – spurring it to respond as if fighting a virus. They did this by stimulating the expression of a protein called PD-L1 inside of tumors, making them more receptive to treatment. The research was supported by multiple federal agencies and foundations, including the National Institutes of Health.
Senior author Elias Sayour, M.D., Ph.D., a UF Health pediatric oncologist, said the results reveal a potential new treatment path – an alternative to surgery, radiation and chemotherapy – with broad implications for battling many types of treatment-resistant tumors.
“This paper describes a very unexpected and exciting observation: that even a vaccine not specific to any particular tumor or virus – so long as it is an mRNA vaccine – could lead to tumor-specific effects,” said Sayour, principal investigator at the RNA Engineering Laboratory within UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy.
“This finding is a proof of concept that these vaccines potentially could be commercialized as universal cancer vaccines to sensitize the immune system against a patient’s individual tumor,” said Sayour, a McKnight Brain Institute investigator and co-leader of a program in immuno-oncology and microbiome research.
Until now, there have been two main ideas in cancer-vaccine development: To find a specific target expressed in many people with cancer, or to tailor a vaccine that is specific to targets expressed within a patient’s own cancer.
This study suggests a third emerging paradigm. What we found is by using a vaccine designed not to target cancer specifically but rather to stimulate a strong immunologic response, we could elicit a very strong anticancer reaction. And so this has significant potential to be broadly used across cancer patients – even possibly leading us to an off-the-shelf cancer vaccine.”
Duane Mitchell, M.D., Ph.D., co-author of the paper
For more than eight years, Sayour has pioneered high-tech anticancer vaccines by combining lipid nanoparticles and mRNA. Short for messenger RNA, mRNA is found inside every cell – including tumor cells – and serves as a blueprint for protein production.
This new study builds upon a breakthrough last year by Sayour’s lab: In a first-ever human clinical trial, an mRNA vaccine quickly reprogrammed the immune system to attack glioblastoma, an aggressive brain tumor with a dismal prognosis. Among the most impressive findings in the four-patient trial was how quickly the new method – which used a “specific” or personalized vaccine made using a patient’s own tumor cells – spurred a vigorous immune-system response to reject the tumor.
In the latest study, Sayour’s research team adapted their technology to test a “generalized” mRNA vaccine – meaning it was not aimed at a specific virus or mutated cells of cancer but engineered simply to prompt a strong immune system response. The mRNA formulation was made similarly to the COVID-19 vaccines, rooted in similar technology, but wasn’t aimed directly at the well-known spike protein of COVID.
In mouse models of melanoma, the team saw promising results in normally treatment-resistant tumors when combining the mRNA formulation with a common immunotherapy drug called a PD-1 inhibitor, a type of monoclonal antibody that attempts to “educate” the immune system that a tumor is foreign, said Sayour, a professor in UF’s Lillian S. Wells Department of Neurosurgery and the Department of Pediatrics in the UF College of Medicine.
Taking the research a step further, in mouse models of skin, bone and brain cancers, the investigators found beneficial effects when testing a different mRNA formulation as a solo treatment. In some models, the tumors were eliminated entirely.
Sayour and colleagues observed that using an mRNA vaccine to activate immune responses seemingly unrelated to cancer could prompt T cells that weren’t working before to actually multiply and kill the cancer if the response spurred by the vaccine is strong enough.
Taken together, the study’s implications are striking, said Mitchell, who directs the UF Clinical and Translational Science Institute and co-directs UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy.
“It could potentially be a universal way of waking up a patient’s own immune response to cancer,” Mitchell said. “And that would be profound if generalizable to human studies.”
The results, he said, show potential for a universal cancer vaccine that could activate the immune system and prime it to work in tandem with checkpoint inhibitor drugs to seize upon cancer – or in some cases, even work on its own to kill cancer.
Now, the research team is working to improve current formulations and move to human clinical trials as rapidly as possible.
Qdaisat, S., et al. (2025). Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading. Nature Biomedical Engineering. doi.org/10.1038/s41551-025-01380-1.
News
Nanoparticle blueprints reveal path to smarter medicines
Lipid nanoparticles (LNPs) are the delivery vehicles of modern medicine, carrying cancer drugs, gene therapies and vaccines into cells. Until recently, many scientists assumed that all LNPs followed more or less the same blueprint, [...]
How nanomedicine and AI are teaming up to tackle neurodegenerative diseases
When I first realized the scale of the challenge posed by neurodegenerative diseases, such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis (ALS), I felt simultaneously humbled and motivated. These disorders are not caused [...]
Self-Organizing Light Could Transform Computing and Communications
USC engineers have demonstrated a new kind of optical device that lets light organize its own route using the principles of thermodynamics. Instead of relying on switches or digital control, the light finds its own [...]
Groundbreaking New Way of Measuring Blood Pressure Could Save Thousands of Lives
A new method that improves the accuracy of interpreting blood pressure measurements taken at the ankle could be vital for individuals who are unable to have their blood pressure measured on the arm. A newly developed [...]
Scientist tackles key roadblock for AI in drug discovery
The drug development pipeline is a costly and lengthy process. Identifying high-quality "hit" compounds—those with high potency, selectivity, and favorable metabolic properties—at the earliest stages is important for reducing cost and accelerating the path [...]
Nanoplastics with environmental coatings can sneak past the skin’s defenses
Plastic is ubiquitous in the modern world, and it's notorious for taking a long time to completely break down in the environment - if it ever does. But even without breaking down completely, plastic [...]
Chernobyl scientists discover black fungus feeding on deadly radiation
It looks pretty sinister, but it might actually be incredibly helpful When reactor number four in Chernobyl exploded, it triggered the worst nuclear disaster in history, one which the surrounding area still has not [...]
Long COVID Is Taking A Silent Toll On Mental Health, Here’s What Experts Say
Months after recovering from COVID-19, many people continue to feel unwell. They speak of exhaustion that doesn’t fade, difficulty breathing, or an unsettling mental haze. What’s becoming increasingly clear is that recovery from the [...]
Study Delivers Cancer Drugs Directly to the Tumor Nucleus
A new peptide-based nanotube treatment sneaks chemo into drug-resistant cancer cells, providing a unique workaround to one of oncology’s toughest hurdles. CiQUS researchers have developed a novel molecular strategy that allows a chemotherapy drug to [...]
Scientists Begin $14.2 Million Project To Decode the Body’s “Hidden Sixth Sense”
An NIH-supported initiative seeks to unravel how the nervous system tracks and regulates the body’s internal organs. How does your brain recognize when it’s time to take a breath, when your blood pressure has [...]
Scientists Discover a New Form of Ice That Shouldn’t Exist
Researchers at the European XFEL and DESY are investigating unusual forms of ice that can exist at room temperature when subjected to extreme pressure. Ice comes in many forms, even when made of nothing but water [...]
Nobel-winning, tiny ‘sponge crystals’ with an astonishing amount of inner space
The 2025 Nobel Prize in chemistry was awarded to Richard Robson, Susumu Kitagawa and Omar Yaghi on Oct. 8, 2025, for the development of metal-organic frameworks, or MOFs, which are tunable crystal structures with extremely [...]
Harnessing Green-Synthesized Nanoparticles for Water Purification
A new review reveals how plant- and microbe-derived nanoparticles can power next-gen water disinfection, delivering cleaner, safer water without the environmental cost of traditional treatments. A recent review published in Nanomaterials highlights the potential of green-synthesized nanomaterials (GSNMs) in [...]
Brainstem damage found to be behind long-lasting effects of severe Covid-19
Damage to the brainstem - the brain's 'control center' - is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests. Using ultra-high-resolution scanners that can see the living brain in [...]
CT scan changes over one year predict outcomes in fibrotic lung disease
Researchers at National Jewish Health have shown that subtle increases in lung scarring, detected by an artificial intelligence-based tool on CT scans taken one year apart, are associated with disease progression and survival in [...]
AI Spots Hidden Signs of Disease Before Symptoms Appear
Researchers suggest that examining the inner workings of cells more closely could help physicians detect diseases earlier and more accurately match patients with effective therapies. Researchers at McGill University have created an artificial intelligence tool capable of uncovering [...]
