Following groundbreaking human trials that successfully reprogrammed the immune system to fight the malignant brain tumor glioblastoma, these scientists have now developed an mRNA vaccine that can fight any kind of cancer. It is expected to replace chemotherapy, surgery and radiation therapy.
University of Florida (UF) scientists have developed an experimental vaccine that significantly boosts the immune system's ability to fight tumors, even if it doesn't target a specific cancer type. This "universal" mRNA vaccine works similarly to the COVID-19 vaccine, but with a different target; it instructs the body's immune cells to assemble and attack any type of tumor like the viral spike protein.
"This paper describes a very unexpected and exciting observation: Even a vaccine that is not targeting any specific tumor or virus—as long as it is an mRNA vaccine—can produce tumor-specific effects," said Elias Sayour, a pediatric oncologist and principal investigator at the University of Florida's RNA Engineering Laboratory. "This finding demonstrates the potential for these vaccines to be commercialized as universal cancer vaccines to sensitize the immune system to a patient's individual tumor."
Sayur has been working for a decade to harness the power of mRNA science to effectively treat cancer. The success of glioblastoma research has expanded the scope of treatments, no longer targeting just a single type of tumor, but focusing on giving the body's immune system the tools to fight any type of cancer cell. Sayur's research is part of growing evidence that mRNA vaccines may be effective weapons in the fight against cancer.
While this formulation is not unlike a COVID-19 vaccine that uses lipid nanoparticles to deliver genetic instructions to the body, there are some differences. The COVID-19 vaccine is not a drug that encodes viral proteins, but sends a message to the immune system, calling on the immune system to unite. Essentially, it tells the body to produce certain proteins that stimulate the immune system, including a protein inside cancer cells called PD-L1 (programmed death ligand 1), which makes tumors more visible to immune cells.
Researchers have discovered a way to induce PD-L1 expression within tumors using a universal mRNA vaccine, essentially tricking cancer cells into exposing themselves, making immunotherapy more effective.
In this study of mice with melanoma, the vaccine was able to clear existing tumors that had proven resistant. In other cancer models, including brain, skin and bone, the drug was able to eliminate tumors even without the aid of any other treatments.
In this field that increasingly pursues personalized medicine and precise targets, this approach is slightly alternative. Previous research has focused more on targeting or customizing vaccines based on a patient's own cancer status.
"This study proposes a third emerging paradigm," said study co-author Duane Mitchell, MD. "We found that by using a vaccine that doesn't specifically target cancer, but instead stimulates a strong immune response, we can elicit a very strong anti-cancer response. So this has potential for broad applications in cancer patients and may even lead to the development of an off-the-shelf cancer vaccine."
In 1993, scientists first discovered how mRNA "instructions" stimulate immune cells in mice, but the main obstacle was how to effectively deliver them into the body. About a decade ago, researchers made a breakthrough by discovering that lipid nanoparticles could effectively deliver extremely fragile mRNA into the body without causing it to break down in the blood.
Now, the technology has advanced rapidly, in part due to the development of COVID-19 vaccines.
The study marks a pivotal moment in cancer immunotherapy, showing how a universal, off-the-shelf mRNA vaccine that does not need to target any specific cancer tumor can awaken the immune system and enhance the effectiveness of existing treatments. By increasing the expression of PD-L1 to expose hidden tumors, researchers have discovered a new pathway that could change the way our bodies fight cancer.
While the vaccine is still being tested in preclinical animal studies, this work lays the foundation for a universal cancer vaccine strategy—one that doesn't rely on tailoring treatments to each patient, but instead teaches the immune system how to fight smarter.
"This could be a universal way to awaken a patient's autoimmune response," Mitchell said. "If it can be extended to human studies, it would have far-reaching implications."
The research was published in the journal Nature Biomedical Engineering.