Following on from their breakthrough human trial that successfully reprogrammed the immune system to overpower glioblastoma, an aggressive brain tumor, the same scientists have now further developed the mRNA vaccine to fight not one but any cancer. It has the potential to do away with chemotherapy, surgery and radiation treatment.
University of Florida (UF) scientists have developed an experimental vaccine that dramatically boosts the immune system’s ability to fight tumors – even without targeting a specific cancer type. This "general purpose" mRNA jab works in a similar way to a Covid-19 vaccine but with a different target; it instructs the body's immune cells to rally and hit any kind of tumor in the same way they would attack a viral spike protein.
“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,” said Elias Sayour, a pediatric oncologist and principal investigator at the RNA Engineering Laboratory at UF. “This finding is a proof of concept that these vaccines potentially could be commercialized as universal cancer vaccines to sensitize the immune system against a patient’s individual tumor."
Sayour has spent a decade working to harness the power of mRNA science in order to effectively treat cancer. The success with the glioblastoma study led to broadening the treatment's scope, not targeting one kind of tumor but instead focusing on giving the body's immune system the tools to fight any kind of cancer cell. It's part of a growing body of evidence that suggests mRNA vaccines might be a serious weapon in fighting the disease.
While the formulation isn't unlike the Covid-19 vaccine, which uses lipid nanoparticles to deliver the genetic instructions to the body, it is still somewhat different. Instead of the drug encoding a virus protein, it sends a message to the immune system to rally the troops. It essentially tells the body to produce certain proteins that stimulate the immune system – including a protein within cancer cells known as PD-L1 (Programmed Death-Ligand 1), which makes tumors become more visible to immune cells.
The researchers found a way to induce PD-L1 expression inside tumors using a generalized mRNA vaccine, essentially tricking the cancer cell into exposing itself, so immunotherapy can be more effective.
In this study on mice with melanoma, the vaccine was able to clear existing tumors that had proven drug-resistant. In other cancer models, including brain, skin and bone, the drug was even able to wipe out tumors without the assistance of any other treatment.
This approach is a little unorthodox in a field moving increasingly more towards personalized medicine with a precise target in the crosshairs. Previous research has focused more on homing in on a target or tailoring a vaccine specific to a patient's own cancer profile.
"This study suggests a third emerging paradigm," said study co-author Duane Mitchell, MD. "What we found is by using a vaccine designed not to target cancer specifically but rather to stimulate a strong immunologic response, we could elicit a very strong anticancer reaction. And so this has significant potential to be broadly used across cancer patients – even possibly leading us to an off-the-shelf cancer vaccine."
Scientists first discovered how mRNA "instruction manuals" could stimulate immune cells (in mice) in 1993, but a major hurdle has been working out how to deliver them into the body effectively. Around a decade ago, a breakthrough came when researchers found that lipid nanoparticles could effectively transport the incredibly fragile mRNA into the body without it being broken down in the bloodstream.
Now, the technology has rapidly advanced, in part due to the development of Covid-19 vaccines.
This study marks a key moment in cancer immunotherapy, demonstrating how a generalized, off-the-shelf mRNA vaccine – not tailored to any specific cancer tumor – can awaken the immune system and amplify the effects of existing treatments. By exposing well-hidden tumors by ramping up PD-L1 expression, the researchers have uncovered a new pathway that could transform how we prime the body to fight cancer.
While the vaccine is still being tested in pre-clinical anima studies, this work lays the foundation for a universal cancer vaccine strategy – one that doesn’t rely on customizing treatment specific to each patient but instead teaches the immune system how to fight smarter.
"It could potentially be a universal way of waking up a patient’s own immune response to cancer," Mitchell said. "And that would be profound if generalizable to human studies."
The research was published in the journal Nature Biomedical Engineering.
Source: University of Florida via EurekAlert
