| Elias Sayour, a pediatric oncologist and mRNA cancer vaccine researcher at the University of Florida, came to his work through a crisis of faith in his own field. A first-generation American whose parents emigrated from Syria, he trained at Duke, drawn to oncology for the relationships it allowed him to forge with his patients: Nobody told him he was spending too long with a patient when that child had cancer. But he wasn’t prepared for how crude the therapies were or what passed as a cure. “We were breaking the first rule of medicine every single time: to cure a fraction, but hurt all ten,” he said. “I thought I was done with medicine, maybe, and that I had chosen the wrong path.” A chance introduction to Dwayne Mitchell, a Duke pioneer in mRNA cell therapy changed his mind and pointed him towards research.
Now, he wants to teach the immune system to catch a chameleon. Cancer, as Sayour describes it, is a masquerading enemy that edits itself to evade detection and subverts the body’s own defenses into a state of tolerance. For the past decade, he has been working to reverse that dynamic using mRNA vaccines. This spring, he was named one of two finalists for the 2026 BioInnovation Institute & Science Prize for Innovation, recognized at a ceremony in Copenhagen for his work developing both personalized and universal mRNA vaccines to mobilize the immune system against cancer.
In his prize essay published in Science, Sayour lays out a new approach to cancer care: universal mRNA vaccines administered before surgery to mobilize immune cells from tumors to draining lymph nodes, followed by immune checkpoint inhibitors or personalized mRNA therapies that can be updated as tumors evolve. “For the chameleon that is cancer will not fool us forever,” he writes. “Though it may change its colors, we too are changing ours.”
ScienceAdviser spoke with Sayour about the unexpected discovery that upended his own assumptions about how mRNA vaccines work and why he thinks the immune system’s response to infection holds the blueprint for beating cancer. Below is that conversation, edited for brevity.
What sparked the discovery of mRNA vaccines priming tumors for treatment?
My project early on during my time at Duke was to create a nanoparticulate delivery system to do what we’re doing outside the body with mRNA inside the body. Very few nanoparticles had actually made it into the clinic, so I really started stratifying what we studied based on nanoparticulate approaches that actually had a chance, and focused on liposomal formulations. I still remember the date of the first nanoparticle experiment working. That feeling is honestly nothing like anything I experienced in medicine. But the reason I had gone back to graduate school, the reason I was doing all of this was: Can we translate it into something? Can we run a clinical trial that actually advances the paradigm?
The discovery that nonspecific mRNA could work was many years later, 2018. And I got to tell you, when all of a sudden you’re seeing these unbelievable responses, we use all different models, melanoma, brain cancer, sarcoma, you name it. And all of a sudden the controls were working. And it’s not like a eureka moment, but more like: Is everything we just published complete crap? Because the whole idea was that mRNA has to be specific. That’s what I had published on. So, it’s a frightening moment. What we came to realize is the bulk of the effects we were seeing, even with personalized vaccines, was really due to nonspecific innate immunity, which suggested you could create a universal vaccine.
In oncology, from the second a patient is diagnosed, you’re on the clock, which is even more true with a pediatric patient. If it’s taking 6, 8, 12-plus weeks to make a personalized vaccine, that’s just time the cancer is evolving. We really believed this could prime an immune response almost immediately. And that preceded the pandemic.
One of my graduate students, who’s now at MD Anderson, asked a very provocative question: If nonspecific mRNA vaccines can sensitize the immune response to immunotherapy, what happens to cancer patients receiving the COVID vaccine? This was a retrospective study (I always have to caution that) but my gosh, the result! There was a near doubling in survival outcome. When he shared those results, the magnitude of the effect really surprised me. Our lab then went back and made the exact COVID vaccine, the exact Pfizer design, because we hadn’t had it, and it worked really well in the animal models. We just published both papers, in tandem, in the last few months.We are now working with MD Anderson Cancer Center to initiate a phase II/III trial to answer this question proactively. And in parallel, we’re engineering a purpose-built universal vaccine.
In my opinion, I think the COVID vaccine is a poorly designed universal cancer vaccine. The coding region, the length, the untranslated regions can all be optimized. We believe we can build something more robust, and we’re hoping to move into a phase I/II trial as the phase II/III gets underway.
What is it about an mRNA vaccine that is so powerful at priming tumors for treatment?
There’s this sense that because the RNA is silenced, it’s not immunogenic. I can tell you, because we’ve studied this, the COVID vaccine is profoundly immunogenic. What I mean by that immunogenicity is the ability to elicit a cytokine-chemokine response that elicits immunologic trafficking. In cancer, the reason a therapeutic cancer vaccine hasn’t worked, even in the context of a specific antigen, is because the tumor microenvironment is immunosuppressed, and there’s also tremendous peripheral tolerance.
I think nature has given us the tools on how to keep the immune system primed and active, and it’s really through infection. mRNA preceded DNA evolutionarily. Any cell that has RNA injected into it elicits a damage response, elicits trafficking of immune cells. So, when you give a COVID vaccine, or any mRNA vaccine, you’re getting a cytokine-chemokine cascade that mobilizes cells from the tumor microenvironments. You have all these immune cells just sitting there in the tumor: some are senescent, some are suppressive, but they have tumor antigens. If you could elicit mobilization of those cells to lymph nodes, and now with the inflammatory orchestra, allow presentation in a manner that can activate a T cell response, you’ve now primed tumor-specific immunity.
The beauty of mRNA is that the orchestra plays. Type 1 interferon is central, we’ve shown that, but there has to be this orchestration of signals. Imagine going to a symphony and seeing all these instruments playing harmoniously. Right now in cancer immunotherapy it’s kind of early days where we’re fumbling around playing one instrument or two, and it sounds like noise. Cancer is so effective at creating immune noise, you just want to tolerate it, ignore it. But if you could create a symphony where each node amplifies the next, you can now truly get breakthrough immunity.
I don’t think we fully understand how to do that yet, but I do think mRNA is a potent tool to initiate that cascade. In and of itself it’s probably not enough. The other thing we’ve been working on is the delivery design. We published a paper a couple of years ago showing that you could aggregate mRNA into almost an onionlike cluster. When we inject that intravenously—holy cow! It’s one of the most immunogenic things. For a tumor like melanoma or lung cancer, maybe we could get away with just the COVID vaccine alone. But for some of the most immune-refractory tumors, we may need to design things in a way that is more aggressive, to shock the immune system back into immunologic function.
What does this prize mean to you?
It feels weird to get recognition for this. It’s very nice, and I’m very grateful and overwhelmed and humbled. But it feels weird because the stories that I’m writing about are patient stories. People who have suffered the unimaginable, who are really the real heroes and who deserve the recognition, not me. I mean, look, I haven’t helped these people. We’re trying to, and unfortunately we do have a long way to go. But I do think progress is being made. Their stories, their inspiration, their fight, that is the foundation of all of this. To see what a pediatric family can do in terms of raising funds, awareness, research, wow! It’s truly heroic. And I wish that was recognized more. |