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Moderna's experimental cancer vaccine treats but doesn't prevent melanoma - a biochemist explains how it works

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A Moderna está testando uma vacina de mRNA em combinação com pembrolizumab para tratar o melanoma.  <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/b48de63f0417e4b5b3s8f4efarc” “https://s.yimg.com/ny/api/res/1.2/16PXtpp0Sm4HgTMAJ8VTow–/YXBwaWQ9aGlnaGxhbmRlcjt3PTcwNTtoPTQ3MA–/https://media.zenfs.com/en/the_conversation_us_articles_815/b48de63f0487e59b31e4e4f”

Media outlets have reported encouraging findings from clinical trials of an experimental new vaccine developed by biotechnology company Moderna to treat an aggressive type of skin cancer called melanoma.

While this is potentially very good news, it occurred to me that headlines can be unintentionally misleading. The vaccines most people are familiar with prevent disease, whereas this new experimental skin cancer vaccine only treats patients who are already sick. Why is it called a vaccine if it doesn’t prevent cancer?

I’m 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 the science. Although preventive and therapeutic vaccines are given for different health goals, they both train the immune system to recognize and fight a specific disease agent that causes the disease.

O melanoma é uma forma agressiva de câncer de pele.  <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_815/932b5d1762ec495d099″ />

How do preventive vaccines work?

Most vaccines are given to healthy people before they get sick to prevent illness caused by viruses or bacteria. This includes vaccines that prevent polio, measles, COVID-19 and many other diseases. Researchers have also developed vaccines to prevent some cancers caused by viruses such as human papillomavirus and Epstein-Barr virus.

Your immune system recognizes objects like certain microbes and allergens that don’t belong in your body and initiates 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 the microbial invader. This results in a cellular memory that will trigger an even faster immune response the next time the same microbe intrudes.

The problem is that sometimes the initial infection causes serious illness before the immune system can mount a response against it. While you might be better protected against a second infection, you suffered the potentially harmful consequences of the first one.

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

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

How does Moderna’s 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 doesn’t prevent cancer like Gardasil-9.

The Moderna vaccine trains the immune system to fight an invader in the same way as the preventative vaccines that 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 composed 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 about which proteins to make. Mutant genes result in abnormal proteins called neoantigens that the body recognizes as foreign. This can trigger an immune response to fight a nascent tumor. However, sometimes the immune response fails to subdue the cancer cells, either because the immune system is unable to mount a strong enough response or because the cancer cells have found a way to bypass the immune system’s defenses.

Moderna’s experimental melanoma vaccine contains genetic information that encodes portions of the neoantigens in the tumor. 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 encodes only small, non-functional parts of the protein. When genetic information is translated into these pieces of protein in the body, they trigger the immune system to mount an attack against the tumor. Ideally, this immune response will cause the tumor to shrink and disappear.

Remarkably, the Moderna melanoma vaccine is tailor-made for each patient. Each tumor is unique and therefore the vaccine also needs to be unique. To customize vaccines, researchers first take a biopsy of the patient’s tumor to determine which neoantigens are present. The vaccine manufacturer then designs specific mRNA molecules that encode these neoantigens. When this personalized mRNA vaccine is administered, the body translates the genetic material into proteins specific to the patient’s tumor, resulting in an immune response against the tumor.

Combining vaccination with immunotherapy

Vaccines are a form of immunotherapy because they treat diseases by taking advantage of the immune system. However, other cancer immunotherapy drugs are not vaccines because, although 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 are two drugs needed?

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

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

It is not a preventive 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 neoantigen profile that cannot be predicted in advance. Therefore, a vaccine cannot be developed before the disease.

The experimental mRNA vaccine against melanoma, still in the early stages of 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 across people and offer personalized therapeutic options against these diseases.

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

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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