University of Florida's mRNA-Based Cancer Vaccine Shows Promise in Mouse Models

Researchers at the University of Florida have developed an experimental mRNA-based cancer vaccine that, when combined with immune checkpoint inhibitors, has demonstrated the ability to eliminate tumors in mouse models. Unlike traditional vaccines targeting specific tumor proteins, this approach stimulates the immune system to respond as if combating a viral infection. The study, published on August 19, 2025, in Nature Biomedical Engineering, reports that the vaccine, either alone or in combination with checkpoint inhibitors, led to significant tumor reduction and, in some cases, complete eradication in models of melanoma, glioma, and metastatic bone cancer. This research suggests potential for a universal, off-the-shelf cancer vaccine applicable across various cancer types.

Traditional cancer vaccines often target specific tumor antigens, requiring personalization for each patient. In contrast, the University of Florida's mRNA vaccine aims to broadly activate the immune system by inducing the expression of the PD-L1 protein within tumors, making them more receptive to treatment. This strategy effectively "wakes up" the immune system, prompting it to attack cancer cells as it would a viral infection.

Dr. 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, led the study. He noted the unexpected nature of the findings, stating, "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."

The research team observed that using an mRNA vaccine to activate immune responses seemingly unrelated to cancer could prompt T cells that weren't working before to multiply and kill the cancer if the response spurred by the vaccine is strong enough. In mouse models of melanoma, the combination of the mRNA vaccine with a common immunotherapy drug called a PD-1 inhibitor showed promising results in normally treatment-resistant tumors. Additionally, in models of skin, bone, and brain cancers, the vaccine alone demonstrated beneficial effects, with some tumors being eliminated entirely.

These findings suggest the possibility of developing a universal cancer vaccine that could be applicable across various cancer types. This would represent a significant advancement over current personalized cancer vaccines, which are tailored to individual patients and can be time-consuming and costly to produce.

Following the promising results in mouse models, the research team plans to initiate human clinical trials to assess the vaccine's safety and efficacy in humans. These trials will be crucial in determining the vaccine's potential as a universal cancer treatment.

The development of mRNA-based cancer vaccines has been an area of active research, especially following the success of mRNA vaccines in combating COVID-19. Companies like Moderna and BioNTech have been exploring personalized mRNA cancer vaccines targeting specific tumor mutations. For instance, Moderna's experimental cancer vaccine, in combination with Merck's checkpoint inhibitor pembrolizumab, has shown promise in reducing the risk of cancer recurrence in melanoma patients.

However, the University of Florida's approach differs by aiming for a universal vaccine that does not require personalization, potentially offering a more efficient and broadly applicable solution.

As the research progresses to human clinical trials, it holds the potential to revolutionize cancer treatment by providing a universal, off-the-shelf vaccine applicable across various cancer types.