Fascinating mouse study hints we may one day have an mRNA vaccine for skin cancer

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Being sun smart could one day include a vaccination similar to the one that currently provides millions of people around the world with immunity to the coronavirus.

While most vaccinations sensitize our immune system to an aggressive agent like a virus even cancer cell, the emerging mRNA vaccine technology could instead train our bodies to generate additional antioxidant proteins, thereby enhancing our ability to protect our DNA from damage caused by sunlight.

A recent study in genetically modified mice by researchers from the United States and Japan confirmed the role of an antioxidant enzyme in protecting against chemical trauma caused by sun exposure.

If the body could be encouraged to make more of the enzyme under the right circumstances, it’s possible that one day such an approach could give us an extra layer of protection against skin cancer.

So far, the concept is largely speculative, with many hurdles to overcome. But given the success of mRNA vaccines in responding to the current pandemic, it’s an option that Oregon State University pharmacologist Arup Indra thinks is rife with possibility.

“For more than 40 years, researchers have considered dietary antioxidants as a possible source of inexpensive, low-risk agents for cancer prevention, but they have not always performed well in clinical trials and, in some cases, they were actually harmful – hence the need to try to intervene with new chemopreventive agents like an mRNA vaccine,” said Indra.

Antioxidants work by interfering with oxidation, a chemical process that results in the loss of electrons from a molecule. For delicate structures like our DNA, this deficiency can lead to chemical changes that greatly increase the risk of cancerous mutations.

High-energy radiation, including frequencies of light in the ultraviolet part of the solar spectrum, does a good job of releasing electrons. Fortunately, we have specialized cells called melanocytes that can produce umbrellas of tanning pigment to shield us from some of this radiation.

Ironically, this pigment production process generates its own oxidative by-products, called reactive oxygen species. It’s a balance that our body strives to keep in check, producing a range of biochemical systems that prevent oxidation.

Thioredoxin reductase 1 (TR1, encoded by the TXNRD1 gene) is a perfect example. Used by melanocytes to compensate for their release of reactive oxygen species, it activates another protein called thioredoxin, which among other things binds reactive oxygen species before they can damage more important structures.

The enzyme reductase has not only been observed at high levels in skin cells after UV exposure, but also in other tissues affected by various cancers, including melanoma. This malignant cancer of the melanocyte is the deadliest of skin cancers, with more than 60,000 people losing their lives to disease every year.

Finding a way to tame oxidative damage early using some of the body’s protective enzymes may well reduce that death toll.

First, though. While TXNRD1 appears to be a good candidate for improving sun protection, the researchers needed to test their hypotheses using a live model.

Knocking out the TXNRD1 gene in mice provided the research team with a way to study the enzyme’s role in pigmentation and the ability of melanocytes to respond to oxidative stress resulting from exposure to ultraviolet radiation- B.

The results were promising, suggesting clear potential in delivering TXNRD1 to skin cells to help promote melanin production and limit damage from sun exposure.

Although much more research would be needed to develop, the messenger RNA encoding this enzyme could be delivered through the body thanks to the type of vaccine technology implemented in the SARS-CoV-2 vaccines produced by Pfizer and Moderna. .

“People at increased risk of skin cancer, such as those who work outdoors in sunny climates, could ideally be vaccinated once a year,” said Indra.

Despite this very early and promising groundwork, there are still many reasons to treat the results with some caution.

Thioredoxin reductases perform a number of tasks in the body related to cell growth. Although they appear to play a role in some aspects of cancer prevention, TXNRD1 has also been shown to contribute to the migration of cancer cells, including in the chest and colorectal carcinomas. It also appears to play a role in spread of melanoma themselves.

Knowing more about its precise activity in cell development and movement could help establish protocols for its safe use as a protective agent.

Optimism for the potential of TXNRD1 aside, the idea of ​​using mRNA vaccines to combat oxidative stress is one that researchers are taking seriously.

“Clearly we are at the tip of the iceberg, but the possibilities are exciting for preventing different types of disease progression, including cancer, by modulating the body’s antioxidant system,” said Indra.

This research was published in the Journal of Investigative Dermatology.

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