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Can mRNA Vaccines Help Treat Cancer?

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The coronavirus pandemic has thrown a spotlight on messenger RNA (mRNA)—the molecule that carries a cell’s instructions for making proteins. Hundreds of millions of people worldwide have received mRNA vaccines that provide powerful protection against severe COVID-19 caused by infection with SARS-CoV-2.

As stunningly successful as the mRNA COVID-19 vaccines have been, researchers have long hoped to use mRNA vaccines for a very different purpose—to treat cancer. mRNA-based cancer treatment vaccines have been tested in small trials for nearly a decade, with some promising early results.

In fact, scientists at both Pfizer-BioNTech and Moderna drew on their experience developing mRNA cancer vaccines to create their coronavirus vaccines. Now, some investigators believe the success of the mRNA COVID-19 vaccines could help accelerate clinical research on mRNA vaccines to treat cancer.

“There’s a lot of enthusiasm around mRNA right now,” said Patrick Ott, M.D., Ph.D., who directs the Center for Personal Cancer Vaccines at the Dana-Farber Cancer Institute. “The funding and resources that are flowing into mRNA vaccine research will help the cancer vaccine field.”

Dozens of clinical trials are testing mRNA treatment vaccines in people with various types of cancer, including pancreatic cancer, colorectal cancer, and melanoma. Some vaccines are being evaluated in combination with drugs that enhance the body’s immune response to tumors.

But no mRNA cancer vaccine has been approved by the US Food and Drug Administration for use either alone or with other cancer treatments.

“mRNA vaccine technology is extremely promising for infectious diseases and may lead to new kinds of vaccines,” said Elad Sharon, M.D., M.P.H., of NCI’s Division of Cancer Treatment and Diagnosis. “For other applications, such as the treatment of cancer, research on mRNA vaccines also appears promising, but these approaches have not yet proven themselves.”

With findings starting to emerge from ongoing clinical trials of mRNA cancer vaccines, researchers could soon learn more about the safety and effectiveness of these treatments, Dr. Sharon added.

How do mRNA vaccines work?

Over the past 30 years, researchers have learned how to engineer stable forms of mRNA and deliver these molecules to the body through vaccines. Once in the body, the mRNA instructs cells that take up the vaccine to produce proteins that may stimulate an immune response against these same proteins when they are present in intact viruses or tumor cells.

Among the cells likely to take up mRNA from a vaccine are dendritic cells, which are the sentinels of the immune system. After taking up and translating the mRNA, dendritic cells present the resulting proteins, or antigens, to immune cells such as T cells, starting the immune response.

“Dendritic cells act as teachers, educating T cells so that they can search for and kill cancer cells or virus-infected cells,” depending on the antigen, said Karine Breckpot, Ph.D., of the Vrije Universiteit Brussel in Belgium, who studies mRNA vaccines.

The mRNA included in the Pfizer-BioNTech and the Moderna coronavirus vaccines instructs cells to produce a version of the “spike” protein that studs the surface of SARS-CoV-2.

The immune system sees the spike protein presented by the dendritic cells as foreign and mobilizes some immune cells to produce antibodies and other immune cells to fight off the apparent infection. Having been exposed to the spike protein free of the virus, the immune system is now prepared, or primed, to react strongly to a subsequent infection with the actual SARS-CoV-2 virus.

Cancer research led to speedy development of mRNA vaccines

When the pandemic struck, mRNA vaccine technology had an unexpected opportunity to demonstrate its promise, said Norbert Pardi, Ph.D., of the University of Pennsylvania Perelman School of Medicine, whose research focuses on mRNA-based vaccines.

“The production of mRNA vaccines today is easy, fast, and can be scaled up as needed,” Dr. Pardi continued. The same manufacturing procedure can be applied to any mRNA sequence, he added.

Historically, the process of developing vaccines has taken 10 to 15 years. But both the Pfizer-BioNTech and the Moderna COVID-19 vaccines—the latter of which was developed in collaboration with NIH—were designed, manufactured, and shown to be safe and effective in people in less than a year.

“To develop an infectious disease vaccine during a pandemic, you need to be fast,” said Lena Kranz, Ph.D., co-director of Cancer Vaccines at BioNTech. “The current pandemic has confirmed our hypothesis that mRNA technology is well suited for fast vaccine development and rapid manufacturing on a global scale.”

The groundwork for the speedy design, manufacturing, and testing of the mRNA COVID-19 vaccines was established through decades of work on cancer vaccines. During this period, immunotherapy, including drugs such as immune checkpoint inhibitors, emerged as a new approach to treating cancer, leading, in some people, to dramatic and long-lasting responses.

“There’s a lot of synergy between research on immunotherapy and mRNA cancer vaccines,” said Robert Meehan, M.D., senior director of clinical development at Moderna. “Vaccines are building on the success of immune checkpoint inhibitors and expanding our knowledge of the underlying biology.”

Modifying and protecting the cargo of mRNA vaccines

Technologies that can deliver mRNA to the body are essential for the success of these vaccines. If an mRNA sequence were injected into the body without some form of protection, the sequence would be recognized by the immune system as a foreign substance and destroyed.

A solution employed by some investigational cancer vaccines is to encase the mRNA in lipid nanoparticles, which are tiny spheres that protect the mRNA molecules. Other delivery vehicles include liposomes, which are also a type of vesicle, or bubble.

“The most advanced mRNA-based vaccine platform uses mRNA encapsulated in lipid nanoparticles,” said Dr. Pardi. Now that the Pfizer-BioNTech and the Moderna coronavirus vaccine trials have demonstrated the effectiveness of lipid nanoparticles, the technology could certainly be used in future cancer vaccine trials, he added.

Another key feature of the Pfizer-BioNTech and the Moderna coronavirus vaccines is the use of modified forms of mRNA, according to Jordan Meier, Ph.D., of NCI’s Center for Cancer Research, who studies mRNA modifications.

The mRNA in these vaccines incorporates pseudouridine, which is a modification of a naturally occurring nucleoside. Nucleosides are the building blocks of mRNA, and the order of specific nucleosides determines the instructions that mRNA gives to the protein-making machinery in cells.

“The [pseudouridine] modification seems to make the mRNA itself almost invisible to the immune system,” said Dr. Meier. The modification does not alter the function of the mRNA but may enhance the effectiveness of the vaccines, he added.

Cancer researchers have been testing both modified and unmodified forms of mRNA in their investigational treatment vaccines. More research is needed to better understand the relative advantages of each approach for the development of cancer vaccines, Dr. Meier said.

Developing and testing personalized mRNA cancer vaccines

For more than a decade, cancer researchers have been developing a type of treatment known as a personalized cancer vaccine using various technologies, including mRNA and protein fragments, or peptides.

The investigational mRNA vaccines are manufactured for individuals based on the specific molecular features of their tumors. It takes 1 to 2 months to produce a personalized mRNA cancer vaccine after tissue samples have been collected from a patient.

“Speed is especially important for individualized cancer vaccination,” said Mathias Vormehr, Ph.D., codirector of Cancer Vaccines at BioNTech. “A highly individualized vaccine combination must be designed and produced within weeks of taking a tumor biopsy.”

With this approach, researchers try to elicit an immune response against abnormal proteins, or neoantigens, produced by cancer cells. Because these proteins are not found on normal cells, they are promising targets for vaccine-induced immune responses.

“Personalized cancer vaccines may teach the immune system how cancer cells are different from the rest of the body,” said Julie Bauman, M.D., deputy director of the University of Arizona Cancer Center.

Dr. Bauman is co-leading a clinical trial testing a personalized mRNA vaccine in combination with an immune checkpoint inhibitor in patients with advanced head and neck cancer. The study initially included patients with colorectal cancer, but this group did not appear to benefit from the therapy.

For patients with head and neck cancer, however, the early results were positive. Among the first 10 participants, 2 patients had all signs of their tumors disappear following treatment, known as a complete response, and another 5 had their tumors shrink.

“We were surprised to see two complete and enduring responses in our first group of patients with head and neck cancers,” said Dr. Bauman, noting that the study has been expanded to include 40 patients with the disease.

“The number of patients treated is small, but we are cautiously optimistic,” she added. The study is sponsored by Moderna, which makes each personalized vaccine in about 6 weeks.

The manufacturing process starts with the identification of genetic mutations in a patient’s tumor cells that could give rise to neoantigens. Computer algorithms then predict which neoantigens are most likely to bind to receptors on T cells and stimulate an immune response. The vaccine can include genetic sequences for up to 34 different neoantigens.

The promise of personalized immunotherapy with mRNA vaccines is “being able to activate T cells that will specifically recognize individual cancer cells based on their abnormal molecular features,” said Dr. Bauman.

Advancing the science of mRNA cancer vaccines

“A lot of immunotherapies stimulate the immune response in a nonspecific way—that is, not directly against the cancer,” said Dr. Ott. “Personalized cancer vaccines can direct the immune response to exactly where it needs to be.”

Some companies are also investigating mRNA cancer vaccines that are based on collections of a few dozen neoantigens that have been linked with certain types of cancer, including prostate cancer, gastrointestinal cancers, and melanoma.

In addition to clinical trials, fundamental research on mRNA cancer vaccines continues. Some investigators are trying to enhance the responses of immune cells to neoantigens in mRNA vaccines. One study, for example, aims to improve the responses of T cells that become exhausted while attacking tumors.

A challenge for the field is learning how best to identify neoantigens for personalized mRNA cancer vaccines, several researchers said.

“There’s still a lot we need to learn and many questions to answer,” Dr. Ott said. It’s not yet clear, for example, how personalized cancer vaccines should be best combined with other treatments, such as immune checkpoint inhibitors, he added.

As cancer researchers pursue these questions, other investigators will be developing knowledge from the growing number of people around the world who are receiving mRNA coronavirus vaccines.

Insights about the composition of mRNA or the way mRNA is packaged that emerge from studies of viruses could potentially inform work on cancer vaccines, said Dr. Breckpot.

“Unfortunately, it took a pandemic for there to be broad acceptance of mRNA vaccines among the scientific community,” she added. “But the global use of COVID-19 mRNA vaccines has demonstrated the safety of this approach and will open doors for cancer vaccines.”

‘Can mRNA Vaccines Help Treat Cancer?’ was originally published by the National Cancer Institute, , by NCI Staff

Pursuing a Cancer Prevention Vaccine

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For more than two decades, Olivera Finn has tirelessly pursued one goal in her research: to develop a vaccine to prevent cancer. She has had this goal since 1989, when her research team discovered the first tumor antigen recognized by a type of immune cell that can kill cancer cells. That antigen—an abnormal version of a protein called MUC1—is produced by the cells of more than 80% of cancer types, including cancers of the breast, pancreas, colon, lung, and prostate.

Although she started her research career as an organ transplant immunologist, the discovery of MUC1 was a pivotal point in Olivera’s career trajectory. “Once we discovered tumor antigens,” she said, “I never looked back.” Olivera received her first NCI grant in 1991 and has been funded ever since to study the biology of tumor antigens and develop them as targets for cancer prevention.

Cancer can take many years—even decades—to develop. Some cancers arise from precursor growths that can be detected by current screening methods. For example, colorectal polyps called advanced adenomas, which can be detected by colonoscopy, can progress to colorectal cancer. These adenomas can be removed surgically, but in many patients, new ones continue to develop and some will become malignant. Olivera’s lab found that the cells of advanced adenomas and the precursors of pancreatic, lung, and many other types of cancer all produce abnormal MUC1 protein.

The presence of abnormal MUC1 on premalignant growths may make it a good target for a vaccine that would prevent their progression to cancer or the development of new precursors. To test this idea, Olivera’s group conducted the first ever clinical trial of a cancer prevention vaccine based on a tumor antigen in healthy people without cancer who were at increased risk of developing the disease.

In the NCI-funded trial, reported in 2013, individuals with a history of advanced adenomas were given an MUC1 vaccine. The vaccine was shown to be safe and to elicit a strong immune response and a long-lasting immune memory. NCI is currently sponsoring a phase II trial testing whether the vaccine will prevent the regrowth of colorectal polyps.

Looking forward, Olivera envisions, “If you are in your 60s and your doctor discovers you are at high risk for cancer, the idea would be to vaccinate to boost the immune system’s ability to keep any abnormal cells in check instead of waiting to see if cancer develops.”

Olivera says that funding from NCI is critical for her research and for cancer prevention research in general. Cancer prevention research is complex, and translating laboratory discoveries into new ways to prevent cancer requires sustained investments over many years—investments that the private sector is often reluctant to make. But “building the evidence that vaccines are an effective way of controlling cancer will go a long way toward getting companies interested,” she said.

The field of cancer immunology has expanded dramatically and has led to immunotherapies for the treatment of advanced cancers as well as vaccines against some viruses that cause cancer. Boosting the immune system to prevent cancers that are not caused by viruses may now be within reach. “The opportunities are amazing,” she added.

 

What is the Future of Cancer Research?

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As we look to the future, the hope of cancer research is to continue to make advances in cancer detection, diagnosis, and patient care that have resulted in people living longer, healthier lives than ever before.

What are Cancer Vaccines?

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Approved Cancer.Net Editorial Board, 08/2020

Vaccines are medicines that help the body fight disease. They can train the immune system to find and destroy harmful germs and cells. There are many vaccines that you receive throughout your life to prevent common illnesses. There are also vaccines for cancer. There are vaccines that prevent cancer and vaccines that treat cancer.

Are there vaccines that prevent cancer?

There are vaccines that can prevent healthy people from getting certain cancers caused by viruses. Like vaccines for the chicken pox or the flu, these vaccines protect the body from these viruses. This type of vaccine will only work if a person gets the vaccine before they are infected with the virus.

There are 2 types of vaccines that prevent cancer approved by the U.S. Food and Drug Administration (FDA):

HPV vaccine. The vaccine protects against the human papillomavirus (HPV). If this virus stays in the body for a long time, it can cause some types of cancer. The FDA has approved HPV vaccines to prevent:

HPV can also cause other cancers the FDA has not approved the vaccine for, such as oral cancer.

Hepatitis B vaccine. This vaccine protects against the hepatitis B virus (HBV). This virus can cause liver cancer.

Are there vaccines that treat cancer?

There are vaccines that treat existing cancer, called treatment vaccines or therapeutic vaccines. These vaccines are a type of cancer treatment called immunotherapy. They work to boost the body’s immune system to fight cancer. Doctors give treatment vaccines to people who already have cancer. Different treatment vaccines work in different ways. They can:

  • Keep the cancer from coming back
  • Destroy any cancer cells still in the body after treatments end
  • Stop a tumor from growing or spreading

How do cancer treatment vaccines work?

Antigens, found on the surface of cells, are substances the body thinks are harmful. The immune system attacks the antigens and, in most cases, gets rid of them. This leaves the immune system with a “memory” that helps it fight those antigens in the future.

Cancer treatment vaccines boost the immune system’s ability to find and destroy antigens. Often, cancer cells have certain molecules called cancer-specific antigens on their surface that healthy cells do not have. When a vaccine gives these molecules to a person, the molecules act as antigens. They tell the immune system to find and destroy cancer cells that have these molecules on their surface.

Some cancer vaccines are personalized. This means they are made for just 1 person. This type of vaccine is produced from samples of the person’s tumor that are removed during surgery. Other cancer vaccines are not personalized and target certain cancer antigens that are not specific to an individual person. Doctors give these vaccines to people whose tumors have those antigens on the surface of the tumor cells.

Most cancer vaccines are only offered through clinical trials, which are research studies that use volunteers. In 2010, the FDA approved sipuleucel-T (Provenge) for people with metastatic prostate cancer, which is prostate cancer that has spread. Sipuleucel-T is tailored to each person through a series of steps:

  • White blood cells are removed from the person’s blood. White blood cells help the body fight infection and disease.
  • The white blood cells are altered in a laboratory to target prostate cancer cells.
  • Next, the doctor puts the altered cells back into the person through a vein. This is similar to a blood transfusion. These modified cells teach the immune system to find and destroy prostate cancer cells.

Another vaccine uses a weakened bacteria called Bacillus Calmette-Guérin (BCG) that is injected into the body. This weakened bacteria activates the immune system to treat early-stage bladder cancer.

What are the challenges of using treatment vaccines?

Making treatment vaccines that work is a challenge because:

Cancer cells suppress the immune system. This is how cancer is able to begin and grow in the first place. Researchers are using adjuvants in vaccines to try to fix this problem. An adjuvant is a substance added to a vaccine to improve the body’s immune response.

Cancer cells start from a person’s own healthy cells. As a result, the cancer cells may not “look” harmful to the immune system. The immune system may ignore the cells instead of finding and fighting them.

Larger or more advanced tumors are hard to get rid of using only a vaccine. This is 1 reason why doctors often give a cancer vaccine along with other treatment.

People who are sick or older can have weak immune systems. Their bodies may not be able to produce a strong immune response after they receive a vaccine. That limits how well a vaccine works. Also, some cancer treatments may weaken a person’s immune system. This limits how well the body can respond to a vaccine.

For these reasons, some researchers think cancer treatment vaccines may work better for smaller tumors or cancer in its early stages.

Vaccines and clinical trials

Clinical trials are key to learning more about both cancer prevention vaccines and cancer treatment vaccines. Researchers are testing vaccines for many types of cancer, including:

Bladder cancer. Researchers are testing how well a vaccine made from a virus altered with the HER2 antigen works. These antigens or molecules live on the surface of some bladder cancer tumors. The virus may help teach the immune system to find and destroy these tumor cells. Researchers also want to know which works better: standard bladder cancer treatment or standard treatment with a vaccine.

Brain tumors. There are many studies testing treatment vaccines aimed at certain molecules on the surface of brain tumor cells. Some focus on newly found brain cancer. Others focus on cancer that has come back, or recurred. Many of the studies include children and teens.

Breast cancer. Many studies are testing treatment vaccines for breast cancer, given alone or with other treatments. Other researchers are working to get vaccines that prevent breast cancer into clinical trials.

Cervical cancer. As explained above, the FDA approved HPV vaccines that prevent cervical cancer. Research continues on vaccines that help treat each stage of cervical cancer.

Colorectal cancer. Researchers are making treatment vaccines that tell the body to attack cells with antigens thought to cause colorectal cancer. These antigens include carcinoembryonic antigen (CEA), MUC1, guanylyl cyclase C, and NY-ESO-1.

Kidney cancer. Researchers are testing many cancer vaccines to treat kidney cancer. They are also testing vaccines to prevent kidney cancer in its later stages from coming back.

Leukemia. Studies are looking at treatment vaccines for various types of leukemia, such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Some are meant to help other treatments, such as a bone marrow/stem cell transplant, work better. Other vaccines made from a person’s cancer cells and other cells may help the immune system destroy the cancer.

Lung cancer. Lung cancer treatment vaccines in clinical trials target antigens.

Melanoma. Researchers are testing many melanoma vaccines, given alone or with other treatments. Destroyed melanoma cells and antigens in the vaccines tell the immune system to destroy other melanoma cells in the body.

Myeloma. There are many clinical trials looking at vaccines for people with multiple myeloma who are near remission. This means doctors can no longer find the cancer in the body and there are no symptoms. Researchers are also testing vaccines in people with smoldering myeloma or who need to have an autologous bone marrow/stem cell transplant.

Pancreatic cancer. Researchers are working on many treatment vaccines designed to boost the immune system’s response to pancreatic cancer cells. The vaccine may be given as the only treatment or along with another treatment.

Prostate cancer. As noted above, sipuleucel-T is a vaccine that doctors can use to treat people with prostate cancer that has spread. Now studies are looking to see if the vaccine can help people with prostate cancer at earlier stages.

Learn more about the latest research for specific cancers in this website’s guides and finding a clinical trial.

Questions to ask your health care team

If you want to learn more about joining a cancer treatment vaccine clinical trial, talk with your health care team. You may want to ask these questions:

  • Is there a clinical trial testing a vaccine for my type and stage of cancer?
  • Where is the clinical trial located?
  • What is the vaccine and how does it work?
  • How is the vaccine made? Will I need blood cells or tumor tissue removed to make the vaccine? How will you remove it?
  • How will I receive the vaccine and how often?
  • How long will I need the vaccine?
  • What side effects could occur?
  • Can I receive the vaccine with other treatments such as radiation therapy or chemotherapy?
  • What are the other treatment options for this cancer?

Related Resources

Getting Treatment in a Clinical Trial

Making Decisions About Cancer Treatment

Clinical Trials

Podcast: Should People With Cancer Be Tested for Hepatitis B?

More Information

National Cancer Institute: Cancer Treatment Vaccines

What are Clinical Trial Phases?

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Clinical trials to test new cancer treatments involve a series of steps, called phases. If a new treatment is successful in one phase, it will proceed to further testing in the next phase.