How mRNA Vaccines Work to Prevent COVID-19 (and Possibly Beat Cancer)

by: Dr. Gabe Mirkin, M.D.

Messenger RNA May Help to Beat Cancer

The two currently-approved COVID-19 vaccines use a technique called messenger RNA (mRNA) that could lead to cures for cancer and many other diseases.

In 2005, Katalin Karikó and Drew Weissman at the University of Pennsylvania discovered that mRNA could be injected to increase a person’s ability to kill germs, but the human immune system would destroy the injected mRNA before it could have any effect on the body. Then they found that they could get the mRNA into cells by encasing it in small bubbles of fat called lipid nanoparticles (LNP).

However, the mRNA researchers did not make any further notable advances against diseases until a major breakthrough occurred in January 2020, when Chinese scientists worked out the structure of the coronavirus that causes COVID-19 and identified the spike protein that lets the virus get into cells.

This breakthrough made it possible to create vaccines with mRNA that would copy the spike protein.

How mRNA Vaccines Work to Prevent COVID-19

• Unlike previous vaccines, the Moderna and Pfizer vaccines do not contain any live or dead viruses, or even parts of a virus. Instead, they both contain mRNA that is made in the laboratory.

• The mRNA that you receive in the vaccine enters some of your cells where the cells’ machinery uses that RNA to make copies of the spike protein of the virus that causes COVID-19.

• The mRNA itself is destroyed within a few hours after it enters your body.

• The spike protein of the coronavirus that you made is a foreign protein, so your immune system recognizes that it is different from you. From then on, if the coronavirus enters your body, your immune system attacks and destroys the spike protein of the coronavirus.

• The spike protein is the key that lets the virus get into your cells. If your immune system destroys the spike protein, the virus cannot get into your cells and it disintegrates very quickly.

• Normally, injecting mRNA would be worthless because the body would destroy it. In the Pfizer and Moderna vaccines, the mRNA is coated with lipid nanoparticles (LNP) that protect the mRNA so it can do its job of making copies of the spike protein.

How mRNA May Be Used to Combat Cancer

The mechanism that is working to immunize people against COVID-19 may also be useful in finding cures for many types of cancer. Cancer cells are different from normal cells. Normal cells go through a certain limited number of doublings and then die. This is called apoptosis. Thus skin cells live 28 days and die, red blood cells live 120 days and then die, and the cells on the inside of your lips live 24 to 48 hours and die, and so forth.

Cancer means that your cells forget that they are supposed to have only a limited lifespan. For example, breast cancer is not fatal as long as it stays in your breast, but when breast cancer cells become so numerous that they spread to your lungs, brain or liver, they can destroy these organ's cells and you die from lung, brain or liver failure. Everybody makes millions of cancer cells every day, but your immune system recognizes that cancer cells are different from normal cells, and seeks out and destroys the cancer cells.

Your immune system destroys cancer cells using a mechanism that is similar to the way that it seeks out and destroys invading germs. Various germs continuously try to invade your body, but your immune system recognizes germs by their surface proteins that are different from your own surface proteins. So when a germ tries to enter your cells, your immune cells and cytokine proteins work to attack and kill the invading germs.

In a like manner, your immune system recognizes that cancer cells are not normal and attacks cancer cells in the same way that it tries to kill germs. If your immune system loses its ability to tell that a cancer cell is different from a normal cell, the cancer cells can multiply, spread through your body and kill you. For many years, scientists have been trying to make copies of cancer cells that can be transmitted with mRNA to restore your immune system's ability to attack and kill those cancer cells. This research is now being accelerated by the recent successes in development of vaccines to combat COVID-19.

Current Research Using mRNA

The research on mRNA over the last 15 years that led to the development of vaccines to treat COVID-19 is also being applied to experimental treatments for many types of cancers.

• Moderna has more than two dozen projects going (some in partnership with Merck and AstraZeneca) to treat cancer, influenza, HIV and heart disease.

• Moderna and Merck are testing an mRNA cancer vaccine in combination with the immunotherapy drug, Keytruda, for colorectal and head and neck cancers.

• BioNTech has several projects to treat cancers, tuberculosis, and influenza. BioNTech recently showed that mRNA may work to combat multiple sclerosis in mice; it has already been shown to cure brain infections in mice (Science, Jan 8, 2021:371(6525):145-153).

• CureVac is studying a cancer treatment using mRNA, AstraZeneca is testing a mRNA treatment for heart failure, and Translate Bio is studying use of mRNA for cystic fibrosis.

• A list of clinical trials using mRNA to treat cancer is available at https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/mrna-based-personalized-cancer-vaccine-mrna-4157