A groundbreaking experimental mRNA vaccine has demonstrated the potential to activate the immune system and eliminate tumors in mouse studies, igniting optimism for the development of a universal cancer vaccine. Rather than focusing on a specific tumor protein, researchers found that enhancing the immune system's response made cancers more susceptible to treatment. When combined with immunotherapy drugs, resistant tumors significantly shrank, and in some cases, the vaccine alone was sufficient to eradicate them.
This innovative mRNA vaccine amplified the tumor-fighting effects of immunotherapy in a study utilizing mouse models, bringing scientists closer to their objective of crafting a universal vaccine to "wake up" the immune system against cancer. This research, published in Nature Biomedical Engineering, was conducted by the University of Florida. The findings revealed that pairing the experimental vaccine with well-known anticancer drugs, specifically immune checkpoint inhibitors, produced a robust antitumor response.
Researchers were astonished to discover that their impressive results stemmed not from targeting a specific protein found in tumors but from simply stimulating the immune system to react as if it were combating a virus. This was achieved by enhancing the expression of a protein called PD-L1 within tumors, thereby increasing their susceptibility to treatment. The research received support from various federal agencies and foundations, including the National Institutes of Health.
Senior author Elias Sayour, M.D., Ph.D., a pediatric oncologist at UF Health, emphasized that these results could pave a new pathway for treatment options beyond traditional methods such as surgery, radiation, and chemotherapy, with significant implications for fighting various types of treatment-resistant tumors.
Dr. Sayour remarks, "This paper describes a very unexpected and exciting observation: that even a vaccine not specific to any particular tumor or virus — as long as it is an mRNA vaccine — could lead to tumor-specific effects." He believes this finding serves as proof of concept, indicating that these vaccines may be developed into universal cancer vaccines capable of sensitizing the immune system against a patient's unique tumor.
Historically, cancer vaccine development has revolved around two primary strategies: identifying a common target expressed in many cancer patients or customizing a vaccine to target specific anomalies within a patient’s cancer. "This study suggests a third emerging paradigm," stated Duane Mitchell, M.D., Ph.D., a co-author of the research. "What we found is that by using a vaccine designed to stimulate a strong immunologic response rather than target cancer specifically, we could provoke a powerful anticancer reaction." This approach holds the potential for widespread applicability across cancer patients, potentially leading to an "off-the-shelf" cancer vaccine.
This latest study builds on a significant breakthrough achieved last year by Sayour’s lab. In a pioneering human clinical trial, an mRNA vaccine effectively reprogrammed the immune system to combat glioblastoma, an aggressive brain tumor with a poor prognosis. Among the most notable outcomes from that trial was the speed at which the personalized vaccine, created from a patient’s tumor cells, rallied a vigorous immune response to reject the tumor.
In the current research, Sayour’s team adapted their technology to evaluate a "generalized" mRNA vaccine — one that was not targeted at a specific virus or cancer mutations but engineered to elicit a robust immune response. The mRNA formulation utilized a similar technology to that of COVID-19 vaccines, though it did not directly target the well-known spike protein associated with COVID-19.
In mouse models of melanoma, the research team observed encouraging outcomes in normally treatment-resistant tumors when the mRNA formulation was combined with a common immunotherapy drug known as a PD-1 inhibitor. This drug serves to "educate" the immune system to recognize tumors as foreign entities. Further exploration in mouse models of skin, bone, and brain cancers revealed beneficial effects when testing a different mRNA formulation as a standalone treatment, with some models resulting in complete tumor elimination.
Sayour and his colleagues noted that employing an mRNA vaccine to prompt immune responses unrelated to cancer could activate previously dormant T cells, encouraging them to proliferate and attack cancer cells, provided the immune response spurred by the vaccine is sufficiently strong. The implications of this study are profound, according to Mitchell, who oversees the UF Clinical and Translational Science Institute and co-directs UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy.
"It could potentially serve as a universal mechanism for awakening a patient’s immune response to cancer," Mitchell stated. "If this can be generalized to human studies, it would be groundbreaking." The findings suggest the potential for a universal cancer vaccine capable of activating the immune system to collaborate with checkpoint inhibitor drugs to combat cancer — and in certain situations, even independently eradicate cancer. The research team is now focused on refining current formulations and expediting the transition to human clinical trials.
Reference: “Sensitization of tumors to immunotherapy by boosting early type-I interferon responses enables epitope spreading” by Sadeem Qdaisat et al., 18 July 2025, Nature Biomedical Engineering. DOI: 10.1038/s41551-025-01380-1
