Scientists at the University of Florida have developed an experimental mRNA vaccine that fights cancer through an unexpected method by stimulating a general immune response rather than attacking specific tumor proteins.
When used in combination with common immunotherapy drugs, the vaccine significantly improved survival in mouse studies, bringing researchers closer to potentially universal cancer treatments.
The study, published in Nature Biomedical Engineering, reveals that the vaccine works by triggering the immune system’s response, just like fighting a virus, even if it doesn’t target any tumor-specific proteins. This counterintuitive strategy enhances the effectiveness of immune checkpoint inhibitors and helps the immune system recognize and destroy drugs that cancer cells.
Resurrection immune response proves effective
A research team led by Dr. Elias Sayour tested the vaccine in a mouse model of melanoma, bone cancer and brain tumors. The results show that when pairing mRNA preparations with PD-1 inhibitors, the results of normal drug-resistant cancers are promising, a common immunotherapy.
“This article describes a very unexpected and exciting observation that even a vaccine for any particular tumor or virus, as long as it is an mRNA vaccine, can lead to tumor-specific effects,” Sayour explained.
The vaccine works by stimulating the expression of a protein called PD-L1 in the tumor, making it more treated. In some mouse models, tumors were completely eliminated when the vaccine was used as an independent treatment.
Destroy traditional vaccine examples
Current cancer vaccine development often follows two approaches: finding targets expressed in many cancer patients, or creating personalized vaccines tailored to individual tumors. This study proposes a third option that can revolutionize the accessibility of treatment.
“What we found was to use a vaccine designed to target cancer specifically, but to stimulate a strong immune response, and we can cause a very strong anti-cancer response,” noted Dr. Duane Mitchell. “So this has great potential for widespread use in cancer patients and may even lead us to a ready-made cancer vaccine.”
This study is based on previous work by Sayour, combining lipid nanoparticles with mRNA technology. Earlier this year, his team reported the success of a personalized mRNA vaccine in a small trial in a glioblastoma patient, achieving rapid immune system activation against this aggressive brain tumor.
The main findings of the study:
- Nonspecific mRNA vaccine enhances the effectiveness of immunotherapy in resistant tumors
- This method triggers “epitope diffusion” – immune recognition of multiple tumor targets
- Some mouse models showed complete elimination of tumors with vaccine only
- The effect depends on early interferon response, rather than tumor-specific targeting
- Technology similar to COVID-19 vaccine, but targets general immune activation
Common methods can change treatment
The most important findings of the study involve a process called epitope diffusion, in which the immune response initially triggered by the vaccine expands to identify and attack actual tumor proteins. This creates a self-amplification effect that can play a role in different cancer types.
The researchers observed that vaccine activation was not previously suitable for cancer T cells. When the immune response produced by the vaccine becomes strong enough, these dormant T cells multiply and begin to effectively kill cancer cells.
“This could be a common way to awaken patients’ immune response to cancer,” Mitchell stressed. “If it could be generalized to human research, it would be profound.”
The team used complex techniques, including two-photon microscopy, to track immune responses and tumor changes. They found that vaccines increase tumor-infiltrating lymphocytes and enhance expression of molecules that help the immune system recognize threats.
The way to human experiments
Unlike traditional cancer vaccines that require identification of specific tumor mutations or proteins, this approach may serve as a “off-the-shelf” treatment. The vaccine uses a technique similar to COVID-19, but targets general immune activation rather than specific viral proteins.
These implications are beyond the current limits of immunotherapy. Many patients with therapeutic tumors respond little to existing checkpoint inhibitors, partly because their immune system is not fully activated by the cancer.
The study addresses the risk gap in cancer treatment, where tumors with low mutation burden (traditionally lower response to immunotherapy) may benefit from artificial immune stimulation. By increasing early interferon response, the vaccine produces diseases that make tumors more vulnerable to immune attacks.
Sayour’s team is now working to refine their formulas and facilitate clinical trials in humans. The potential of a universal cancer vaccine that activates dormant immune response is a significant shift from current precise drug approaches to broader immunological strategies.
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