How mRNA vaccines could transform skin cancer treatment
As mRNA innovations race forward researchers are now looking at ways to create skin cancer vaccines using the novel technology. A new study from Oregon State University proposes mRNA-induced production of a specific protein may prevent melanoma, while mRNA pioneer BioNTech is already up to Phase 2 human trials for its unique skin cancer vaccine.
Before 2020, mRNA vaccine technology was still unproven, despite promising early preclinical work and preliminary human trials. The COVID-19 pandemic hit fast-forward on this innovative research and now, in 2022, billions of people have successfully and safely been administered with mRNA vaccines.
Researchers also looking at how mRNA technology could help fight a variety of other diseases, from HIV and malaria to shingles and the Epstein-Barr virus. One of the more compelling areas of research at the moment is work targeting perhaps the most common disease facing humanity today – cancer.
BioNTech, responsible for the initial development of the first mRNA COVID-19 vaccine ultimately licensed by Pfizer, has a broad assortment of cancer-related mRNA treatments in development. From colorectal, pancreatic and ovarian cancers, to a number of general solid tumor treatments, BioNTech is at the head of the pack in terms of mRNA cancer treatment. And its melanoma treatment is perhaps its most advanced mRNA candidate.
Dubbed BNT111 the therapeutic mRNA vaccine is part of a platform of treatments under the name FixVac. These FixVac treatments focus on specific cancer types known to consistently display the same antigens in a large number of patients.
BNT111 focuses on four particular melanoma antigens. The company says at least one of those four antigens can be found in more than 90 percent of skin cancers.
Phase 1 trials found BNT111 to be safe, with promising early signs of efficacy in a small cohort of advanced melanoma patients. In mid-2021 a larger Phase 2 trial commenced with a plan to enroll 180 patients and test the efficacy of BNT111 administered in combination with an experimental monoclonal antibody called Libtayo.
No results from this Phase 2 trial have been announced to date. However, in November 2021 the US Food and Drug Administration (FDA) granted BNT111 a Fast Track Designation. This FDA process is designed to expedite development of treatments showing promising early clinical data.
BioNTech’s melanoma vaccine is a therapeutic vaccine, meaning it is not designed to prevent skin cancer but instead is hoped to work as an immunotherapy treatment in patients already diagnosed with the disease. A new study from researchers at Oregon State University (OSU) is suggesting it could be possible to create a prophylactic mRNA skin cancer vaccine that actually prevents the disease from developing in the first place.
The OSU research focuses on an enzyme called thioredoxin reductase 1 (TR1). This molecule plays an important antioxidant role in skin cells, protecting them from oxidative stress and DNA damage caused by ultraviolet radiation.
Across several preclinical experiments outlined in the new study, the researchers demonstrated how TR1 can directly prevent UV damage in skins cells that would lead to cancer. Arup Indra, lead researcher on the project, says a mRNA vaccine that stimulates production of TR1 could hypothetically help prevent skin cancer from developing.
“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,” says Indra. “People at increased risk of skin cancer, such as those who work outside in sunny climates, could ideally be vaccinated once a year.”
At the moment the OSU research is largely hypothetical. While animal studies have demonstrated TR1 can prevent UV-induced DNA damage there are plenty of steps ahead for the researchers before this idea becomes a real vaccine. But Indra suggests there is extraordinary potential for mRNA therapeutics to influence antioxidant systems and work as a prophylactic cancer vaccine.
“Everything needs to be tested and validated in preclinical models,” explains 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.”
The new OSU research was published in the Journal of Investigative Dermatology.