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mRNA Vaccine for Skin Cancer Effective in Mouse Model

Every year we get the flu shot, and it’s looking like we may need to add an annual COVID-19 shot to the docket as well. If you spend a lot of time in the sun or have a genetic history of skin cancer—the most common cancer in the United States—researchers at Oregon State University are working to add another vaccine to your list.

In a mouse model, a mRNA vaccine that promotes production of the protein TR1 in skin cells was effective in mitigating the risk of UV-induced cancers and other skin problems, according to new research published in the Journal of Investigative Dermatology.

“For more than 40 years researchers have looked at 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 have actually been harmful,” said Arup Indra, professor of pharmaceutical sciences at OSU and the study’s leader. “Hence the need to try to intervene with new chemoprevention agents, such as an mRNA vaccine.”

Melanoma, the most lethal type of skin cancer, is a form in which malignant cells form in skin cells, known as melanocytes. TR1, short for thioredoxin reductase 1, is a key component of melanocytes’ antioxidant system. Antioxidants offer protection from reactive oxygen species (ROS) that are on the hunt for electrons from molecules in cells and can damage DNA.

Melanocytes are under ROS siege not only from the sun but also because the process of making pigment causes ROS to be produced too. By catalyzing the transfer of electrons, antioxidants work like an off switch for what would otherwise be a chain reaction affecting multiple molecules in melanocytes and other cells, thereby preventing oxidation.

Messenger RNA vaccines work by instructing cells to make a particular protein. In the case of the coronavirus vaccines, it’s a harmless piece of the virus’ spike protein, which triggers an immune response. For the proposed melanoma vaccine, it would be TR1.

“Following uptake of the mRNA into the cell and the cell’s machinery going to work, the cell should be at a high antioxidant level and able to take care of oxidative stress and DNA damage arising from ultraviolet radiation,” Indra said. “People at increased risk of skin cancer, such as those who work outside in sunny climates, could ideally be vaccinated once a year.”

Since they observed increased oxidative stress and DNA damage without TR1, despite the presence of other antioxidant proteins, Indra and his team believe a vaccine for only TR1 would be sufficient. However, they are not ruling out the possibility that other antioxidants, such as glutathione peroxidase and superoxide dismutase, could also be important.

“Everything needs to be tested and validated in preclinical models,” said Indra. “We need to generate an mRNA vaccine, have it delivered locally or systematically and then monitor how it boosts the body’s defenses. Clearly we’re at the tip of the iceberg but the possibilities are exciting for preventing different types of disease progression including cancer by modulating the bodies’ antioxidant system.”

Details

  • Corvallis, OR 97331, USA
  • Arup Indra