Cancer treatment vaccines are a type of immunotherapy that treats cancer by strengthening the body’s natural defenses against the cancer. Unlike cancer prevention vaccines, cancer treatment vaccines are designed to be used in people who already have cancer—they work against cancer cells, not against something that causes cancer.

The idea behind treatment vaccines is that cancer cells contain substances, called tumor-associated antigens, that are not present in normal cells or, if present, are at lower levels. Treatment vaccines can help the immune system learn to recognize and react to these antigens and destroy cancer cells that contain them.

Cancer treatment vaccines may be made in three main ways.

1. They can be made from your own tumor cells. This means they are custom-made so that they cause an immune response against features that are unique to your cancer.
2. They may be made from tumor-associated antigens that are found on cancer cells of many people with a specific type of cancer. Such a vaccine can cause an immune response in any patient whose cancer produces that antigen. This type of vaccine is still experimental.
3. They may be made from your own dendritic cells, which are a type of immune cell. Dendritic cell vaccines stimulate your immune system to respond to an antigen on tumor cells. One dendritic cell vaccine has been approved, sipuleucel-T, which is used to treat some men with advanced prostate cancer.

A different type of cancer treatment, called oncolytic virus therapy, is sometimes described as a type of cancer treatment vaccine. It uses an oncolytic virus, which is a virus that infects and breaks down cancer cells but does not harm normal cells.

The first FDA-approved oncolytic virus therapy is talimogene laherparepvec (T-VEC, or Imlygic®). It is based on herpes simplex virus type 1. Although this virus can infect both cancer and normal cells, normal cells are able to kill the virus while cancer cells cannot.

T-VEC is injected directly into a tumor. As the virus makes more and more copies of itself, it causes cancer cells to burst and die. The dying cells release new viruses and other substances that can cause an immune response against cancer cells throughout the body.

A protein or other molecule that is found only on cancer cells and not on normal cells. Tumor-specific antigens can help the body make an immune response against cancer cells. They may be used as possible targets for targeted therapy or for immunotherapy to help boost the body’s immune system to kill more cancer cells. Tumor-specific antigens may also be used in laboratory tests to help diagnose some types of cancer.

For more than a century, doctors have been interested in using viruses to treat cancer, and in recent years a small but growing number of patients have begun to benefit from this approach.

Some viruses tend to infect and kill tumor cells. Known as oncolytic viruses, this group includes viruses found in nature as well as viruses modified in the laboratory to reproduce efficiently in cancer cells without harming healthy cells.

To date, only one oncolytic virus—a genetically modified form of a herpesvirus for treating melanoma—has been approved by the Food and Drug Administration (FDA), though a number of viruses are being evaluated as potential treatments for cancer in clinical trials.

Oncolytic viruses have long been viewed as tools for directly killing cancer cells. But a growing body of research suggests that some oncolytic viruses may work—at least in part—by triggering an immune response in the body against the cancer.

When a virus infects a tumor cell, the virus makes copies of itself until the cell bursts. The dying cancer cell releases materials, such as tumor antigens, that allow the cancer to be recognized, or “seen,” by the immune system.

“Oncolytic viruses are alerting the immune system that something’s wrong,” said Jason Chesney, M.D., Ph.D., director of the University of Louisville’s James Graham Brown Cancer Center. This can lead to an immune response against nearby tumor cells (a local response) or tumor cells in other parts of the body (a systemic response).

For this reason, some researchers consider oncolytic viruses to be a form of immunotherapy—a treatment that harnesses the immune system against cancer. But many in the field would agree that more studies are needed to learn how different oncolytic viruses work against cancer.

A Modern Approach to an Old Idea

Since the late 1800s, doctors have observed that some patients with cancer go into remission, if only temporarily, after a viral infection. Today, several dozen viruses—and a few strains of bacteria—are being studied as potential cancer treatments, according to research presented at an NCI-sponsored conference on using microbes as cancer therapies in 2017.

“Oncolytic virus therapy is of growing interest to researchers for one reason: It’s working,” said Juan Fueyo, M.D., of the University of Texas MD Anderson Cancer Center, who co-developed a type of oncolytic virus being tested in patients with brain tumors.

Although the notion of using viruses in cancer therapy is old, the science only began to move forward in the 1990s with advances in genetic engineering technology, noted Matthias Gromeier, M.D., of the Duke Cancer Institute, who has led clinical trials of a genetically modified form of poliovirus.

“There was another shift—around 2005—as people began to realize that the true value of viruses in cancer therapy is in immunotherapy,” Dr. Gromeier continued. “Today, viruses are firmly established as a potential option to enhance and mediate immunotherapy.”

He added: “These are still early days for oncolytic viruses, but it’s now getting interesting.”

The First FDA-Approved Oncolytic Virus Therapy

The first oncolytic virus to receive FDA approval was a treatment for melanoma known as talimogene laherparepvec (Imlygic), or T-VEC. The treatment, which is injected into tumors, was engineered to produce a protein that stimulates the production of immune cells in the body and to reduce the risk of causing herpes.

In some patients receiving the therapy, tumors that could not be injected have shrunk, suggesting that T-VEC can generate a systemic immune response, noted Howard Kaufman, M.D., of the Rutgers Cancer Institute of New Jersey.

“The oncolytic virus kills tumor cells and causes the release of danger signals, which help to generate an immune response,” explained Dr. Kaufman, who co-led the clinical trial that led to the approval of T-VEC.

Investigating Interactions with the Immune System

At the NCI meeting about using microbes as cancer therapies last year, more than 350 investigators discussed many topics, including the need to better understand how infectious agents interact with tumors and with components of the immune system.

The biological mechanisms used by viruses to kill tumors depend on various factors, including the virus, the target tissue or cell, and which biological pathways are targeted, according to Phillip Daschner of NCI’s Division of Cancer Biology, who helped organize the NCI conference.

Some viruses work primarily by killing tumor cells, whereas others work by directing local or systemic immune responses, he explained. Nonetheless, “there was a consensus at the meeting that even for directly oncolytic therapies, there probably is an important immune component to the response,” he added.

Dr. Kaufman noted that T-VEC, when given alone or in combination with other therapies, generally has been well tolerated by patients in clinical trials.

“We continue to be impressed by the safety profile of these approaches,” he said. “The quality of life for many of these patients is barely affected by these agents.”

Using Viruses to Enhance the Body’s Immune Response

One of the challenges for researchers now is to try to enhance the immune response to the tumor through a variety of strategies, including by combining oncolytic virus therapy and immunotherapy.

The promise of this approach has been demonstrated in two early-phase clinical trials. Patients with melanoma who received T-VEC plus a type of immunotherapy known as a checkpoint inhibitor had higher response rates than those who received a checkpoint inhibitor alone.

In one trial, nearly 200 patients received T-VEC with or without ipilimumab (Yervoy®). The results suggested to the researchers that the combination therapy could induce an immune response. “To me, that’s the big finding of this study,” said Dr. Chesney, who co-led the clinical trial with Dr. Kaufman.

In the second trial, which included 21 patients, T-VEC was combined with pembrolizumab (Keytruda®). The oncolytic virus induced the infiltration of immune cells known as T cells into tumors that had low levels of these cells prior to treatment, the researchers found.

The study suggests that the viral therapy can change the local microenvironment to make an immunologically “cold” tumor—that is, a tumor lacking T cells—into an inflamed, or “hot,” tumor, noted John B.A.G. Haanen, Ph.D., of the Netherlands Cancer Institute in a commentary accompanying the study results.

“The injection [of T-VEC] is like lighting a match—it’s the spark that starts a fire,” said Antoni Ribas, M.D., Ph.D., of the UCLA Jonsson Comprehensive Cancer Center, who led the trial. The therapy was generally well tolerated, he noted, and the most common side effects were fatigue, fever, and chills.

A phase 3 clinical trial involving 600 patients with melanoma who will receive T-VEC with or without pembrolizumab is under way to assess the combination therapy in a large, randomized study.

The same combination—T-VEC plus pembrolizumab—is also being evaluated in a clinical trial for patients with advanced melanoma that has progressed despite treatment with a checkpoint inhibitor such as pembrolizumab or nivolumab (Opdivo®).

This NCI-sponsored trial is testing the idea that injections of T-VEC into accessible melanoma tumors will increase the infiltration of immune cells into these and potentially other tumors, making them susceptible to treatment with pembrolizumab.

A New Way of Delivering Viruses

Most oncolytic virus therapies have been tested in patients with melanoma or brain tumors, and most treatments have been given as injections into tumors. Two new studies highlight efforts to expand the number of cancer types treated with oncolytic virus therapies as well as the methods of delivery.

One of the studies found that an oncolytic virus delivered intravenously could cross the blood–brain barrier and enter brain tumors, killing tumor cells. The treatment uses a type of virus known as a reovirus, which causes mild symptoms of a cold or stomach bug in children.

In the second study, researchers tested the Maraba virus, which was originally isolated from a species of sand fly in Brazil, as a way to sensitize tumors to immunotherapy in a mouse model of triple-negative breast cancer.

In both studies, the researchers found that giving oncolytic virus therapy prior to surgery may alter the body’s immune response and enhance the effects of subsequent treatment with a checkpoint inhibitor.

“Combination immunotherapies like these may be most effective when used early in treatment when tumor burden is less and immune systems are intact,” noted Marie-Claude Bourgeois-Daigneault, Ph.D., of the University of Ottawa, an investigator on the Maraba virus study.

Testing a Modified Form of Poliovirus against Brain Tumors

At the Duke Cancer Institute, Dr. Gromeier and his colleagues have been testing an engineered poliovirus, called PVS-RIPO, in patients with glioblastoma.

When the research began in the mid-1990s, Dr. Gromeier viewed oncolytic viruses primarily as agents for killing cancer cells. His thinking changed, however, as PVS-RIPO was tested in patients, and his team noticed clinical changes associated with immune responses in the patients.

“From the first patients, we observed very clear signs that the virus elicited antitumor immune responses,” Dr. Gromeier recalled. Some patients had swelling in the brain and “profound changes in the tumor that took months to develop, which is consistent with an immune event,” he explained.

Based on the results of the clinical studies, FDA in 2016 granted “breakthrough status” to Duke’s poliovirus therapy, which allows officials at FDA to accelerate the agency’s review of the therapy for approval.

“We are interested in exploring what we can combine with PVS-RIPO,” said Dr. Gromeier. “Everyone seems to agree that no single mode of treatment will do the trick in treating cancer.”

A phase 2 trial testing PVS-RIPO with or without the chemotherapy drug lomustine (Gleostine®) is under way in patients with glioblastoma.

Investigating the Mechanisms of Oncolytic Virus Therapy

To learn more about the mechanisms by which poliovirus therapy attacks tumor cells, the Duke researchers recently conducted experiments in cancer cell lines and in mice.

They found that cancer cells infected with PVS-RIPO released tumor antigens and other material that activated immune cells called dendritic cells and induced an immune response against the cancer cells.

“In the mouse model, we showed that a poliovirus could induce a T-cell response that recognizes the tumor,” said Smita Nair, Ph.D., of the Duke University School of Medicine. The finding provides further support for testing the oncolytic virus in combination with other types of immunotherapies, including checkpoint inhibitors, she added.

The Duke team is planning a clinical trial to test PVS-RIPO in six patients with triple-negative breast cancer. Two weeks before undergoing surgery, the patients will receive injections of the treatment into their tumors and will be followed to determine whether the poliovirus triggers any changes in immune system molecules or in the tumor.

Future Research Questions and Priorities for the Field

As oncolytic viruses are tested in clinical trials, researchers will try to learn which patients are likely to respond. “We need biomarkers to help develop effective combination therapies and to select patients who are most likely to benefit from certain combinations,” said Dr. Nair.

Another challenge for the field will be to use the knowledge gained from the melanoma clinical trials to develop treatments for patients with other types of tumors, Dr. Chesney noted.

For researchers, it will also be important to understand “how much tumor infection and killing is required to treat cancer,” said Dr. Gromeier. “These are critical questions that we need to answer, and we’re working on it.”

Oncolytic Viruses May Also Reveal Insights into Immunotherapy

Research on oncolytic viruses may yield insights into the use of current immunotherapies.

“Viruses are great tools for helping us to understand how the antitumor immune response works,” said Dr. Fueyo of MD Anderson. “What we learn from viruses will help us move the field of immunotherapy forward.”

The evolution in thinking about oncolytic viruses since Dr. Fueyo began working in the field two decades ago represents an important shift that has implications for future research.

“We used to think only about making viruses better—more powerful—at killing tumor cells,” said Dr. Fueyo. “Now we need to find ways to help viruses enhance the immune response.”

Sipuleucel-T is used to treat men with prostate cancer:

• that has spread to other parts of the body
• who have few or no symptoms
• whose cancer does not respond to hormone treatment

T-VEC is used to treat some patients with melanoma that returns after surgery and cannot be removed with more surgery.

Cancer treatment vaccines can cause side effects, which affect people in different ways. The side effects you may have and how they make you feel will depend on how healthy you are before treatment, your type of cancer, how advanced it is, the type of treatment vaccine you are getting, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how serious they will be. So, it is important to know which signs to look for and what to do if you start to have problems.

Cancer treatment vaccines can cause flu-like symptoms, which include:

• fever
• chills
• weakness
• dizziness
• nausea or vomiting
• muscle or joint aches
• fatigue
• headache
• trouble breathing
• low or high blood pressure

You may have a severe allergic reaction.

Sipuleucel-T can cause stroke.

T-VEC can cause tumor lysis syndrome. In this syndrome, the tumor cells die and break apart in the blood. This changes certain chemicals in the blood, which may cause damage to organs like the kidneys, heart, and liver.

Since T-VEC is made from herpesvirus it can sometimes cause a herpesvirus infection that can lead to:

• pain, burning, or tingling in a blister around the mouth, genitals, fingers, or ears
• eye pain, sensitivity, discharge from the eyes, and blurry vision
• weakness in the arms and legs
• extreme fatigue and drowsiness
• confusion

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.” 

At a Glance

• A personalized mRNA vaccine against pancreatic cancer created a strong anti-tumor immune response in half the participants in a small study.
• The vaccine will soon be tested in a larger clinical trial. The approach may also have potential for treating other deadly cancer types.

An experimental vaccine for pancreatic cancer showed progress against the disease. MattL_Images / Shutterstock

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is one of the deadliest cancer types. Despite modern therapies, only about 12% of people diagnosed with this cancer will be alive five years after treatment.

Immunotherapies—drugs that help the body’s immune system attack tumors—have revolutionized the treatment of many tumor types. But to date, they have proven ineffective in PDAC. Whether pancreatic cancer cells produce neoantigens—proteins that can be effectively targeted by the immune system—hasn’t been clear.

An NIH-funded research team led by Dr. Vinod Balachandran from Memorial Sloan Kettering Cancer Center (MSKCC) have been developing a personalized mRNA cancer-treatment vaccine approach. It is designed to help immune cells recognize specific neoantigens on patients’ pancreatic cancer cells. Results from a small clinical trial of their experimental treatment were published on May 10, 2023, in Nature.

After surgery to remove PDAC, the team sent tumor samples from 19 people to partners at BioNTech, the company that produced one of the COVID-19 mRNA vaccines. BioNTech performed gene sequencing on the tumors to find proteins that might trigger an immune response. They then used that information to create a personalized mRNA vaccine for each patient. Each vaccine targeted up to 20 neoantigens.

Customized vaccines were successfully created for 18 of the 19 study participants. The process, from surgery to delivery of the first dose of the vaccine, took an average of about nine weeks.

All patients received a drug called atezolizumab before vaccination. This drug, called an immune checkpoint inhibitor, prevents cancer cells from suppressing the immune system. The vaccine was then given in nine doses over several months. After the first eight doses, study participants also started standard chemotherapy drugs for PDAC, followed by a ninth booster dose.

Sixteen volunteers stayed healthy enough to receive at least some of the vaccine doses. In half these patients, the vaccines activated powerful immune cells, called T cells, that could recognize the pancreatic cancer specific to the patient. To track the T cells made after vaccination, the research team developed a novel computational strategy with the lab of Dr. Benjamin Greenbaum at MSKCC. Their analysis showed that T cells that recognized the neoantigens were not found in the blood before vaccination. Among the eight patients with strong immune responses, half had T cells target more than one vaccine neoantigen.

By a year and a half after treatment, the cancer had not returned in any of the people who had a strong T cell response to the vaccine. In contrast, among those whose immune systems didn’t respond to the vaccine, the cancer recurred within an average of just over a year. In one patient with a strong response, T cells produced by the vaccine even appeared to eliminate a small tumor that had spread to the liver. These results suggest that the T cells activated by the vaccines kept the pancreatic cancers in check.

“It’s exciting to see that a personalized vaccine could enlist the immune system to fight pancreatic cancer—which urgently needs better treatments,” Balachandran says. “It’s also motivating as we may be able to use such personalized vaccines to treat other deadly cancers.”

More work is needed to understand why half the people did not have a strong immune response to their personalized vaccines. The researchers are currently planning to launch a larger clinical trial of the vaccine.

—by Sharon Reynolds