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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 in laboratory mice.
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 and the Stop Children's Cancer/Bonnie R. Freeman Professor for Pediatric Oncology Research, said the results reveal a potential future 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,” said Duane Mitchell, M.D., Ph.D., a co-author of the paper. “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.” 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.
While the experimental mRNA vaccine at this point is in early preclinical testing — in mice not humans — information about available nonrelated human clinical trials at UF Health can be viewed here.
For centuries, scholars and scientists have defined the “good life” in one of two ways: a life that is rooted in happiness, characterized by positive emotions, or one that is centered on meaning, guided by purpose and personal fulfillment. But what if there is another, equally valuable path — one that prioritizes challenge, change and curiosity?
“We found that what was missing was psychological richness — experiences that challenge you, change your perspective and satisfy your curiosity.” — Erin Westgate, Ph.D., assistant professor psychology, director of the Florida Social Cognition and Emotion Lab This third dimension, which may result in a more psychologically rich life for some, is being explored in a new study — led by University of Florida psychologist Erin Westgate, Ph.D., in collaboration with Shigehiro Oishi, Ph.D., of the University of Chicago. According to their research, some people prioritize variety, novelty and intellectually stimulating experiences, even when those experiences are difficult, unpleasant or lack clear meaning.
“This idea came from the question: Why do some people feel unfulfilled even when they have happy and meaningful lives?” Westgate said. “We found that what was missing was psychological richness — experiences that challenge you, change your perspective and satisfy your curiosity.” Westgate and Oishi’s research shows that a psychologically rich life is distinct from lives defined by happiness or meaning. While happiness focuses on feeling good, and meaning is about doing good, richness is about thinking deeply and seeing the world differently. And for a significant minority of people around the world, that third path is the one they would choose — even if it means giving up happiness or meaning.
A new way to think about the ‘good life’ According to Westgate and Oishi, psychological richness is defined as a life filled with diverse, perspective-changing experiences — whether these are external, such as traveling or undertaking new challenges, or internal, like absorbing powerful books or pieces of music.
“A psychologically rich life can come from something as simple as reading a great novel or hearing a haunting song,” Westgate said. “It doesn’t have to be about dramatic events, but it can shift the way you see the world.” Unlike happy or meaningful experiences, rich experiences are not always pleasant or purposeful.
“College is a good example. It’s not always fun, and you might not always feel a deep sense of meaning, but it changes how you think,” Westgate said. “The same goes for experiences like living through a hurricane. You wouldn’t call it happy or even meaningful, but it shakes up your perspective.” Researchers in Westgate’s lab at UF have been studying how people respond to events like hurricanes, tracking students’ emotions and reactions as storms approach. The results show that many people have viewed these challenging experiences as psychologically rich — altering how they saw the world, even if they didn’t enjoy them.
The roots of the idea While the study is new, the concept has been years in the making. Westgate and Oishi first introduced the term “psychologically rich life” in 2022, building on earlier research and scale development around 2015. Their latest paper expands the idea, showing that the concept resonates with people across cultures and fills a gap in how people define well-being.
“In psychology and philosophy, dating back to Aristotle, there’s been a focus on hedonic versus eudaimonic well-being — happiness versus meaning,” Westgate said. “What we’re doing is saying, there’s another path that’s just as important. And for some people, it’s the one they value most.” While many people ideally want all three — happiness, meaning and richness — there are trade-offs. Rich experiences often come at the cost of comfort or clarity.
“Interesting experiences aren’t always pleasant experiences,” Westgate said. “But they’re the ones that help us grow and see the world in new ways.”
Westgate hopes the study will broaden how psychologists and the public think about what it means to live well.
“We’re not saying happiness and meaning aren’t important,” Westgate said. “They are. But we’re also saying don’t forget about richness. Some of the most important experiences in life are the ones that challenge us, that surprise us and that make us see the world differently.”
For millions of viewers, “Love Island” has been a summer obsession – a chance to peek in on a sunny villa full of beautiful singles looking for love. But according to Andrew Selepak, Ph.D., a media professor at the University of Florida, the reality show isn’t really about romance.
“The reality of reality TV is that it doesn’t reflect reality,” Selepak said. “These are people who were selected; they were cast just like you would cast a movie or a scripted TV show.” Still, what happens on the island isn’t completely disconnected from real life. The show's format, which is built on snap decisions, physical attraction, and frequent recouplings, mirrors the current dating landscape in unsettling ways.
“I think it's reflective of the current culture that young people are experiencing with dating, which is very superficial and doesn't lead to long-term lasting relationships because a long-term lasting relationship can't be based on superficial qualities,” Selepak said. Selepak compares “Love Island” to “TV Tinder.” Much like on dating apps, contestants size each other up based on looks and vibes rather than values or long-term compatibility. And while the show promotes the idea of finding “the one,” the numbers tell a different story.
“It’s like less than 12% of the couples actually remain together for any period of time,” Selepak said. “At some point, you would think people would realize it’s fake.” However, viewers continue to watch, and contestants continue to sign up. Why? Because the point isn't necessarily to find love. It's about visibility, likes and followers.
“This is where you have the social media aspect playing in, where people are looking to become influencers and to gain fame, notoriety, likes and follows,” Selepak said. “The people who are on the shows, these are people who intentionally have gone out and said, 'I want my dirty laundry to be on TV.’ There's a narcissistic aspect of wanting to be on a show like that. Most people, I think, would be hesitant to tell their deep, dark secrets – or tell the things about themselves that they would normally only share with a select few – to a large audience.” For contestants, this often means performing love rather than experiencing it – a behavior that echoes real-world dating on social media.
For audiences, “Love Island” gives them the dissatisfaction of watching beautiful people experience the same dating struggles they do. In the end, “Love Island” may not teach us how to find lasting love, but it might explain why so many people are struggling to.
