Scientists from the University of Florida and the University of Texas MD Anderson Cancer Center have made a groundbreaking discovery while exploring the potential of mRNA-based therapies to activate the immune system against cancer. This research builds on over a decade of work focused on how messenger RNA (mRNA) can be leveraged to awaken the body’s natural defenses against malignant cells. The findings bring us closer to realizing the concept of a universal cancer vaccine, which could significantly enhance the effectiveness of existing immunotherapy drugs.
An analysis of more than 1,000 patient records at MD Anderson provided crucial data supporting these observations. Although the results are preliminary, the research team is now in the process of designing a randomized clinical trial to validate their findings.
The implications of this discovery are nothing short of extraordinary. Co-senior author Elias Sayour, M.D., Ph.D., a pediatric oncologist at UF Health, remarked, “This could revolutionize the entire field of oncologic care. We could create a more effective, nonspecific vaccine designed to mobilize and reset the immune response, potentially serving as a universal, off-the-shelf cancer vaccine for all patients.”
Jeff Coller, Ph.D., an expert in mRNA and a professor at Johns Hopkins University, emphasized the significance of this discovery, highlighting how Operation Warp Speed—the federal initiative that accelerated the development of COVID-19 vaccines—continues to yield unexpected benefits for Americans. “The results from this study demonstrate the powerful potential of mRNA medicines in revolutionizing cancer treatment,” he stated.
Published on October 22 in the journal Nature, this research builds on Sayour’s eight years of work integrating lipid nanoparticles with mRNA technology. mRNA is a vital component found in all cells that delivers instructions for protein synthesis. Earlier in July, Sayour's lab made a surprising discovery: a robust immune attack on tumors could be triggered without targeting a specific protein within the cancer cells. Instead, simply stimulating the immune system, akin to its response to a virus, could suffice for generating an antitumor effect.
In laboratory experiments, Sayour’s team found that combining their experimental nonspecific mRNA vaccine with a class of anticancer drugs, known as immune checkpoint inhibitors, led to a powerful immune response in mice. Remarkably, the experimental vaccine did not target the COVID spike protein or any other specific molecule; it utilized the same foundational technology as COVID vaccines but functioned more broadly.
This discovery, years in the making, prompted a question from former lab member and first author Adam Grippin, M.D., Ph.D., who trained at UF's Preston A. Wells Center for Brain Tumor Therapy and is now affiliated with MD Anderson. He wondered whether the COVID-19 mRNA vaccine could operate similarly to the nonspecific vaccine. To investigate, the research team analyzed existing data from patients with Stage 3 and 4 non-small cell lung cancer and metastatic melanoma treated at MD Anderson between 2019 and 2023. Their findings revealed that receiving a COVID mRNA vaccine within 100 days of starting immunotherapy drugs was associated with significantly longer survival rates.
Sayour noted the most striking difference was observed in patients who were not expected to have a strong immune response based on their tumor’s molecular characteristics and other factors. While the findings are based on observational data and require confirmation through a prospective randomized clinical trial, they represent a pivotal moment in cancer treatment.
In the realm of lung and skin cancers, doctors often stimulate the immune system using drugs aimed at enhancing its ability to recognize and attack cancer cells. However, in advanced disease stages, many patients do not respond well and frequently exhaust other treatment options, such as radiation, surgery, and chemotherapy. The new study analyzed records of 180 advanced lung cancer patients who received a COVID vaccine within a 100-day window before or after starting immunotherapy drugs, alongside 704 patients treated with the same drugs who did not receive the vaccine. The findings indicated that receiving the vaccine was associated with a near doubling of median survival, from 20.6 months to 37.3 months.
Among the metastatic melanoma patients, 43 received a vaccine within 100 days of beginning immunotherapy, while 167 patients did not. For those vaccinated, median survival increased from 26.7 months to a range of 30 to 40 months; at the time of data collection, some patients remained alive, suggesting that the vaccine's impact could be even more profound.
To bolster their findings, UF scientists conducted experiments in mice combining immunotherapy drugs with an mRNA vaccine explicitly targeting the COVID spike protein. The results indicated that this combination could convert previously treatment-resistant tumors into ones that responded effectively, halting tumor growth. Sayour explained, “When you administer an mRNA vaccine, it acts as a flare, mobilizing immune cells from less effective areas like the tumor to more productive zones like the lymph nodes.”
The next step involves launching a large clinical trial through the UF-led OneFlorida+ Clinical Research Network, a consortium of hospitals and health centers across Florida, Alabama, Georgia, Arkansas, California, and Minnesota. Dr. Betsy Shenkman, who leads the consortium, noted, “One of our key motivations at OneFlorida is to transition discoveries from academic settings into real-world applications where patients receive care.”
If confirmed, these new findings could unlock numerous possibilities in cancer treatment. Researchers believe that an even better nonspecific universal vaccine could be developed. For patients battling advanced cancers, the potential increase in survival from such a universal vaccine could provide an invaluable benefit: more time to spend with loved ones and to explore additional treatment options. Sayour emphasized, “If we can double what we are achieving currently, or even achieve a modest incremental increase—5%, 10%—that means a lot to those patients, especially if this can be applied across various cancers and different patients.”
This pivotal study was supported by the National Cancer Institute and several foundations. Sayour, Grippin, and Mitchell hold patents related to UF-developed mRNA vaccines that are licensed by iOncologi Inc., a biotech company that emerged as a spinout from UF, in which Mitchell has an interest.
