Can a vaccine be the solution to the surge in melanoma cases caused by the climate crisis?

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Melanoma vaccine

Melanoma is the most serious type of skin cancer, and is primarily caused by too much exposure to ultraviolet (UV) light – in the U.K., around 85% of melanomas are thought to be caused by too much ultraviolet radiation. And, unfortunately, because of this, the surge in global temperatures caused by the climate crisis is now resulting in a surge in melanoma cases. 

Given the cause of melanoma, it’s easy to see why the climate crisis is exacerbating the issue, as rising temperatures, thinning of the ozone layer, and increased sun exposure, all play their part in the increasing rates of melanoma. In fact, it is projected that a 2 °C (3.6°F) increase in ambient temperature could increase skin cancer incidence by 11% globally by 2050.

And, as the effects of climate change show no signs of slowing down, and heatwaves are likely to become more frequent, improving the treatment options for melanoma is now a necessity that could save many lives. 

“The earth is getting warmer and skin exposed to warmer temperatures does increase the odds of melanoma. I do believe that whenever we can accelerate the development of new cancer drugs, it represents a big opportunity,” commented Jonathan Lakey, advisor at CancerVax.

The current standard of care for melanoma often involves surgery to completely remove the tumor, along with some surrounding tissue, to try and ensure that no cancer cells remain.

According to Thomas Marron, director of the Early Phase Trials Unit at the Tisch Cancer Institute and associate professor of medicine at the Icahn School of Medicine at Mount Sinai, immunotherapy is also a standard of care treatment for metastatic melanoma, either given as a monotherapy or in combination with other therapies. 

“This has revolutionized the treatment for melanoma, with nearly half of patients going into remission and staying in remission; a far cry from where we were prior to the advent of immunotherapy, where all patients with metastatic melanoma died, and the chemotherapy we used was very toxic and minimally effective at controlling the disease,” said Marron.

However, even though standard of care immunotherapy treatments are helping to cure what over a decade ago seemed incurable, more than half of patients will still succumb to their cancer. 

There is hope in sight though, as personalized mRNA vaccines have made great strides since COVID-19 and are now being tested as cancer vaccines, with the technology proving to be extremely promising for the treatment of melanoma in particular. 

Moderna’s personalized vaccine shows great promise for melanoma  

Moderna is, of course, well-known for its Spikevax mRNA vaccine against COVID-19, and now the company is also developing a personalized cancer vaccine that, in a small clinical trial, showed very promising results against advanced melanoma in patients who had undergone surgery for their cancer, but who had a very high risk of their cancer returning.

Similar to Moderna’s COVID-19 vaccine, this vaccine delivered mRNA wrapped in lipid nanoparticles into cells, instructing them to make a protein, which, in this case, involved up to 34 tumor neoantigens (foreign proteins that are absent in normal tissues, but can arise from tumors through various mechanisms) per patient. Essentially, this means that the vaccine teaches the immune system to recognize 34 different things that are unique to this particular cancer, ultimately improving the chances of success.

All participants in the phase 2 trial received Merck’s immunotherapy Keytruda (pembrolizumab), which is the standard of care for high-risk melanoma patients, while two-thirds also received Moderna’s melanoma vaccine. The results concluded that the combination of the two treatments reduced the risk of recurrence by nearly half, with patients who received both the vaccine and Keytruda more likely to remain cancer-free 18 months later than those who did not receive the vaccine.

“The standard of care right now is to just receive pembrolizumab, but adding the vaccine to the pembrolizumab significantly decreased the likelihood that their cancer comes back. While the data are too new to know the final outcome, we postulate that this improvement will translate to a much higher cure rate than would be achieved with surgery and immunotherapy alone,” said Marron.

The statistics from the study certainly suggest this could be the case: 40% of the patients who only received Keytruda had a recurrence of their cancer during the two-year follow up, while just 22.4% of patients who received both Keytruda and the melanoma vaccine had a recurrence. 

Furthermore, these results are potentially a milestone for the cancer vaccine field, as this is the first time a cancer vaccine has actually been shown to have this level of benefit.  

BioNTech’s melanoma vaccine in phase 2 trials 

BioNTech is also working on the development of a potentially promising mRNA melanoma vaccine, known as BNT111, which is currently being investigated in a phase 2 trial in patients with anti-PD1-refractory/relapsed unresectable Stage 3 or 4 melanoma. This vaccine is also being tested in combination with another drug; this time, the monoclonal antibody medication cemiplimab.

The phase 1 study was completed this year, with final biomarker and clinical data of the trial being gathered and evaluated. But, initial data from the phase 1 dose-escalation trial showed a favorable safety profile and preliminary anti-tumor responses for BNT111 treatment in patients with advanced melanoma.

BNT111 received orphan drug designation from the U.S. Food and Drug Administration (FDA) in September 2021, as well as fast track status in November 2021, which the company said underlines the potential of its FixVac vaccine platform to address the current treatment challenges of melanoma. 

Combination therapies could hold the key

As can be seen with Moderna’s and BioNTech’s melanoma vaccine trials, combination therapies involving a cancer vaccine and another immunotherapy drug might be the best way forward for the treatment of melanoma and other types of cancer.

“I believe the combination is key to the efficacy we are seeing, as the vaccine teaches the immune system what to recognize, but it is the keytruda that takes the brakes off the immune system and enables the strongest, most potent vaccinal response against the cancer. While cancer vaccines alone have been shown to work in some instances, the greatest benefit will come from combinatorial approaches such as this,” said Marron, commenting on Moderna’s vaccine trial.

But, Lakey said that, although it’s great that combination therapies can be so effective, he also hopes that monotherapies can become just as effective when used on their own. “Combination therapies are commonplace today when treating cancer, even when using chemotherapy. With Moderna’s drug in particular, I think it is wonderful that they have positive data using Keytruda in combination with other drugs. I believe that we can always improve on standard of care. Therefore, I’m hopeful that this leads to single therapies that can be as, or more, effective. But, I’m encouraged that Moderna has a treatment regimen that is showing positive results.” 

Whether used in combination with other drugs, or on their own, what does seem clear is that mRNA technology is now leading the way when it comes to cancer vaccines, with several mRNA vaccine candidates advancing into clinical studies and inducing positive clinical responses in early stage trials, particularly against melanoma. 

“I am a big believer in mRNA technologies. I agree that it has come a long way in recent times, and it is very exciting to see the progress. I hope (and believe) that it will continue to produce positive results in the oncology field and with other diseases,” said Lakey. 

And, as Moderna’s personalized cancer vaccine enters into phase 3 of clinical trials, we could soon see the benefit of this technology for the treatment of melanoma, which could arrive just in time, as the planet hurtles towards breaching the key 1.5°C warming threshold.

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