The University of Florida has made a groundbreaking discovery in the development of a new cancer vaccine. Researchers have successfully used an experimental mRNA vaccine to boost the tumor-fighting effects of immunotherapy in mouse-model studies. This breakthrough brings them one step closer to their goal of creating a universal vaccine that can “wake up” the immune system against cancer.

The study, published in Nature Biomedical Engineering, demonstrated that pairing the test vaccine with common anticancer drugs called immune checkpoint inhibitors triggered a strong antitumor response. What’s surprising is that this promising result was achieved by simply revving up the immune system – spurring it to respond as if fighting a virus – rather than attacking a specific target protein expressed in the tumor.

The research team, led by senior author Elias Sayour, M.D., Ph.D., used an mRNA vaccine to stimulate the expression of a protein called PD-L1 inside tumors, making them more receptive to treatment. This innovative approach has broad implications for battling many types of treatment-resistant tumors.

“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 Sayour, principal investigator at the RNA Engineering Laboratory within UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy.

The study suggests a third emerging paradigm in cancer-vaccine development: using a vaccine designed not to target cancer specifically but rather to stimulate a strong immunologic response, which can elicit a very strong anticancer reaction. This has significant potential to be broadly used across cancer patients – even possibly leading us to an off-the-shelf cancer vaccine.

For more than eight years, Sayour has pioneered high-tech anticancer vaccines by combining lipid nanoparticles and mRNA. The new study builds upon a breakthrough last year by Sayour’s lab: In a first-ever human clinical trial, an mRNA vaccine quickly reprogrammed the immune system to attack glioblastoma, an aggressive brain tumor with a dismal prognosis.

The research team adapted their technology to test a “generalized” mRNA vaccine – meaning it was not aimed at a specific virus or mutated cells of cancer but engineered simply to prompt a strong immune system response. The mRNA formulation was made similarly to the COVID-19 vaccines, rooted in similar technology, but wasn’t aimed directly at the well-known spike protein of COVID.

In mouse models of melanoma, the team saw promising results when combining the mRNA formulation with a common immunotherapy drug called a PD-1 inhibitor. In some models, the tumors were eliminated entirely.

The study’s implications are striking, said co-author Duane Mitchell, M.D., Ph.D.: “It could potentially be a universal way of waking up a patient’s own immune response to cancer.” The research team is working to improve current formulations and move to human clinical trials as rapidly as possible.

A new study published in The Journal of Immunology has made an intriguing discovery about how a parasitic worm evades detection and what it can teach us about pain relief. Researchers from Tulane School of Medicine found that the Schistosoma mansoni worm, which causes schistosomiasis, suppresses neurons in the skin to avoid triggering an immune response.

When this worm penetrates human skin, typically through contact with infested water, it produces molecules that block a protein called TRPV1+, which is responsible for sending pain signals to the brain. This clever mechanism allows the worm to infect the skin largely undetected.

The researchers believe that the S. mansoni worm evolved this strategy to enhance its own survival and found that blocking TRPV1+ also reduced disease severity in mice infected with the parasite. The study suggests that identifying the molecules responsible for suppressing TRPV1+ could lead to new painkillers that do not rely on opioids.

Moreover, the researchers discovered that TRPV1+ is essential for initiating host protection against S. mansoni infection. When this protein is activated, it triggers a rapid mobilization of immune cells, which induces inflammation and helps fight off the parasite. This finding highlights the critical role of neurons in pain-sensing and immune responses.

The study’s lead author, Dr. De’Broski R. Herbert, emphasizes that identifying these molecules could inform preventive treatments for schistosomiasis. He envisions a topical agent that activates TRPV1+ to prevent infection from contaminated water for individuals at risk of acquiring S. mansoni.

This groundbreaking research has the potential to revolutionize our understanding of pain relief and immune responses, offering new avenues for developing innovative therapies that could benefit millions worldwide.

The article “Flossing for Vaccines: A New Method to Deliver Immunizations” discusses a novel technique developed by researchers to deliver vaccines via dental floss. The method targets the junctional epithelium, a thin layer of tissue between the tooth and gum, which lacks barrier features and is more permeable than other epithelial tissues. This allows for enhanced antibody production across the body’s mucosal layers.

The researchers applied vaccine-coated floss to lab mice and compared antibody production in three different methods: via the junctional epithelium, nasal epithelium, or under the tongue. They found that applying vaccine via the junctional epithelium produced a superior antibody response on mucosal surfaces than the current gold standard for vaccinating via the oral cavity.

This technique has significant advantages beyond improved antibody response on mucosal surfaces. It is easy to administer and addresses concerns many people have about being vaccinated with needles. The researchers also believe this method should be comparable in price to other vaccine delivery techniques.

However, there are some drawbacks to consider. This technique would not work on infants and toddlers who do not yet have teeth. Additionally, the approach may not be suitable for people with gum disease or other oral infections, and more research is needed to fully understand its potential benefits and limitations.

The study was published in the journal Nature Biomedical Engineering and was supported by grants from the National Institutes of Health and funds from the Whitacre Endowed Chair in Science and Engineering at Texas Tech University. The researchers are optimistic about this work and may move toward clinical trials depending on their findings.