Moderna’s experimental cancer vaccine treats but doesn’t prevent melanoma – biochemist explains how it works

Moderna teste un vaccin à ARNm en association avec le pembrolizumab pour traiter le mélanome.  <a href=Javier Zayas Photography/Moment via Getty Images” src=”https://s.yimg.com/ny/api/res/1.2/16PXtpp0Sm4HgTMAJ8VTow–/YXBwaWQ9aGlnaGxhbmRlcjt3PTcwNTtoPTQ3MA–/https://media.zenfs.com/en/the_conversation_us_articles_815/b48de63f0487e59b35be4fefa88″ datafefa88″ datafefa88″ “https://s.yimg.com/ny/api/res/1.2/16PXtpp0Sm4HgTMAJ8VTow–/YXBwaWQ9aGlnaGxhbmRlcjt3PTcwNTtoPTQ3MA–/https://media.zenfs.com/en/the_conversation_us_articles_815/b48de63f0487e59b31e4efa85b/”1efa85b/>

The media has reported encouraging results from clinical trials of a new experimental vaccine developed by biotech company Moderna to treat an aggressive type of skin cancer called melanoma.

While this is potentially very good news, it occurred to me that the headlines could be unintentionally misleading. Vaccines that most people are familiar with prevent disease, while this experimental new skin cancer vaccine only treats patients who are already sick. Why is it called a vaccine if it does not prevent cancer?

I am a biochemist and molecular biologist who studies the roles that microbes play in health and disease. I also teach cancer genetics to medical students and am interested in how the public understands science. While preventive and therapeutic vaccines are given for different health care purposes, they both train the immune system to recognize and fight off a specific pathogen that causes disease.

Le mélanome est une forme agressive de cancer de la peau.  <a href=Callista Images/Image source via Getty Images” data-src=”https://s.yimg.com/ny/api/res/1.2/9RDq_m0Ww5jg.P3phD10eA–/YXBwaWQ9aGlnaGxhbmRlcjt3PTcwNTtoPTQ3MA–/https://media.zenfs.com/en/the_conversation_us_articles_815/932b5d17630909ec2945d4e” />

How do preventive vaccines work?

Most vaccines are given to healthy people before they get sick to prevent illnesses caused by viruses or bacteria. These include vaccines that prevent poliomyelitis, measles, COVID-19 and many other diseases. Researchers have also developed vaccines to prevent certain types of cancers caused by viruses such as human papillomaviruses and Epstein-Barr virus.

Your immune system recognizes things like certain germs and allergens that don’t belong in your body and triggers a series of cellular events to attack and destroy them. Thus, a virus or bacteria that enters the body is recognized as something foreign and triggers an immune response to fight off the microbial invader. This results in a cellular memory that will trigger an even faster immune response the next time the same microbe enters.

The problem is that sometimes the initial infection causes serious illness before the immune system can react against it. Although you may be better protected against a second infection, you have suffered the potentially damaging consequences of the first.

This is where preventive vaccines come in. By introducing a harmless version or part of the microbe into the immune system, the body can learn to mount an effective response against it without causing disease.

For example, the Gardasil-9 vaccine protects against the human papilloma virus, or HPV, which causes cervical cancer. It contains protein components present in the virus that cannot cause disease, but trigger an immune response that protects against future HPV infection, thus preventing cervical cancer.

How does the Moderna cancer vaccine work?

Unlike cervical cancer, cutaneous melanoma is not caused by a viral infection, according to the latest evidence. Moderna’s experimental vaccine also does not prevent cancer like Gardasil-9 does.

The Moderna vaccine trains the immune system to fight off an invader the same way preventative vaccines most people are familiar with. However, in this case, the invader is a tumor, a rogue version of normal cells that harbors abnormal proteins that the immune system can recognize as foreign and attack.

What are these abnormal proteins and where do they come from?

All cells are made up of proteins and other biological molecules such as carbohydrates, lipids and nucleic acids. Cancer is caused by mutations in regions of genetic material, or DNA, that encode instructions for proteins to be made. Mutated genes produce abnormal proteins called neoantigens that the body recognizes as foreign. This can trigger an immune response to fight off an incipient tumor. However, sometimes the immune response fails to get the cancer cells under control, either because the immune system is unable to mount a strong enough response or because the cancer cells have found a way around the immune system’s defenses.

Moderna’s experimental melanoma vaccine contains genetic information that codes for parts of the tumor’s neoantigens. This genetic information is in the form of mRNA, which is the same form used in the Moderna and Pfizer-BioNtech COVID-19 vaccines. Importantly, the vaccine cannot cause cancer because it only codes for small, non-functional parts of the protein. When genetic information is translated into these bits of protein in the body, it triggers the immune system to mount an attack on the tumor. Ideally, this immune response will cause the tumor to shrink and disappear.

Notably, the Moderna melanoma vaccine is tailor-made for each patient. Each tumor is unique and therefore the vaccine must be unique as well. To customize vaccines, researchers first perform a biopsy of the patient’s tumor to determine which neoantigens are present. The vaccine maker then designs specific mRNA molecules that code for these neo-antigens. When this personalized mRNA vaccine is given, the body translates the genetic material into proteins specific to the patient’s tumor, which leads to an immune response against the tumor.

Combining vaccination with immunotherapy

Vaccines are a form of immunotherapy because they treat disease by harnessing the immune system. However, other immunotherapy cancer drugs are not vaccines because, while they also stimulate the immune system, they do not target specific neoantigens.

In fact, the Moderna vaccine is co-administered with the immunotherapy drug pembrolizumab, marketed as Keytruda. Why do you need two drugs?

Certain immune cells called T cells have molecular accelerator and brake components that serve as checkpoints to ensure that they are only activated in the presence of a foreign invader such as a tumor. However, tumor cells sometimes find a way to maintain T-cell brakes and suppress the immune response. In these cases, the Moderna vaccine correctly identifies the tumor, but the T cells cannot respond to it.

Pembrolizumab, however, can bind directly to a braking component on the T cell, inactivating the braking system and allowing immune cells to attack the tumor.

Not a preventative cancer vaccine

So why can’t the Moderna vaccine be given to healthy people to prevent melanoma before it appears?

Cancers vary greatly from person to person. Each melanoma harbors a different neo-antigen profile that cannot be predicted in advance. Therefore, a vaccine cannot be developed before the disease.

The experimental melanoma mRNA vaccine, currently still in early stage clinical trials, is an example of the new frontier of personalized medicine. By understanding the molecular basis of diseases, researchers can explore how their underlying causes vary from person to person and provide personalized treatment options for these diseases.

This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. If you found it interesting, you can subscribe to our weekly newsletter.

It was written by: Mark R. O’Brian, University at Buffalo.

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Mark R. O’Brian receives funding from the National Institutes of Health.

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