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. 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.

Source: https://www.cancer.gov/

Cancer cells have a series of features that allow the immune system to identify and attack them. However, these same cells create an environment that blocks immune cells and protects the tumour. This means that immune cells cannot reach the cancer cells to remove them. The scientific community has been working for years to increase the effectiveness of the immune system against cancer by using vaccines based on dead tumour cells.

Scientists at IRB Barcelona, led by ICREA researcher Dr. Manuel Serrano, and Dr. Federico Pietrocola, now at the Karolinska Institutet, in Sweden, have studied how inducing senescence in cancer cells improves the effectiveness of the immune response to a greater degree than the dead cancer cells. After vaccinating healthy mice with senescent cancer cells and then stimulating the formation of tumours, the researchers observed that the animals did not develop cancer or that the number that do is significantly reduced. They also analysed the efficacy of vaccination in animals that had already developed tumours. In this setting, although the results were more moderate due to the protective barrier of the tumour, improvements were also observed.

"Our results indicate that senescent cells are a preferred option when it comes to stimulating the immune system against cancer, and they pave the way to considering vaccination with these cells as a possible therapy," explains Dr. Serrano, head of the Cellular Plasticity and Disease lab at IRB Barcelona.

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 A new way to significantly increase the potency of almost any vaccine has been developed by researchers from the International Institute for Nanotechnology (IIN) at Northwestern University.

The scientists used chemistry and nanotechnology to change the structural location of adjuvants and antigens on and within a nanoscale vaccine, greatly increasing vaccine performance. The antigen targets the immune system, and the adjuvant is a stimulator that increases the effectiveness of the antigen. 

 “The work shows that vaccine structure and not just the components is a critical factor in determining vaccine efficacy,” said lead investigator Chad A. Mirkin, director of the IIN. “Where and how we position the antigens and adjuvant within a single architecture markedly changes how the immune system recognizes and processes it."

This new heightened emphasis on structure has the potential to improve the effectiveness of conventional cancer vaccines, which historically have not worked well, Mirkin said. 

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Two major pharmaceutical companies are testing a personalized vaccine that might prevent the recurrence of a specific type of skin cancer. Moderna, one of the companies behind the COVID-19 vaccine, and Merck, an enterprise focused largely on oncology and preventative medicines, are teaming up to see if they can reduce the public’s risk of re-developing the deadliest form of skin cancer: melanoma.

The vaccine essentially combines two medical technologies: the mRNA vaccine and Merck’s Keytruda. As with the COVID-19 vaccine, mRNA shots don’t require an actual virus. Instead, they use a disease’s genetic code to “teach” the immune system to recognize and fight that particular illness. This makes it relatively easy and inexpensive for scientists to develop mRNA vaccines and edit them if a new form of the disease emerges. Keytruda, meanwhile, is a prescription medication that helps prevent melanoma from coming back after known cancer cells have been surgically removed.

Moderna and Merck are testing the feasibility of not only creating a two-in-one drug with both technologies but also customizing individual vaccines to suit their respective patients. Each vaccine is engineered to activate the patient’s immune system, which in turn deploys T cells (a type of white blood cell known to fight cancer) that go after the specific mutations of a patient’s tumor. Keytruda assists this effort by barring certain cell proteins from getting in the way of T cells’ intervention.

The experimental drug is currently in its second clinical trial out of three. The trial involves 157 participants with high-risk melanoma who just successfully underwent surgical removal. Some of the participants were given the personalized vaccine, while others were given Keytruda alone. Moderna and Merck will observe whether the participants’ melanoma returns over the span of approximately one year, with primary data expected at the end of this year.

If a vaccine preventing the recurrence of melanoma does in fact become commercially available, it could prevent more than 7,000 deaths per year in the US alone.

Source: https://www.extremetech.com/

After surgery to remove tumors, some cancer cells can be left behind where they can grow back or spread to a new part of the body. Researchers at the University of Wisconsin-Madison have now developed a hydrogel that can be applied post-surgery to prevent or slow tumor regrowth. The gel works by releasing two compounds selected to strategically keep cancer from coming back after surgery. First is a drug called Pexidartinib, which is already in use to inhibit tumor-associated macrophages (TAMs). These are immune cells that have, for unclear reasons, “switched sides” and now contribute to creating a pro-cancer environment. As such, inhibiting these TAMs slows the growth (or regrowth) of cancer.

A microscope image of the hydrogel (teal) containing platelets with antibodies (red) and tumor-fighting drug nanoparticles (green)

The second component is made up of PD-1 antibodies, which help train T cells to recognize and attack cancer cells. These are bound to platelets for stability. Together, the two components prevent the formation of a microenvironment that’s favorable to cancer growth, and help the immune system clear out any cancer cells remaining after surgery. After its work is done, the gel is designed to biodegrade safely in the body.

The researchers tested the gel in mouse models of several different types of cancers, including colon cancer, melanoma, sarcoma, and triple negative breast cancer. The gel significantly reduced recurrence and metastasis of the cancer, and extended the survival rates of the mice – all control animals succumbed within 36 days, while survival rates ranged between 50 and 66 percent for treated mice, depending on the type of cancer.

The local application of the gel also helps prevent side effects that can arise if a drug is delivered system-wide. As such, no major side effects were seen in the test mice. Importantly, the team says that some of these cancers don’t usually respond well to immune therapy, and are prone to metastasizing, so the effectiveness of the gel treatment is encouraging.

“We are really glad to see that this local strategy can work against so many different kinds of tumors, especially these non-immunogenic tumors,” said Quanyin Hu, lead researcher on the study. “We are even more glad to see this local treatment can inhibit tumor metastasis.”

Source: https://newatlas.com/

Until recently, most of the world had never heard of mRNA vaccines. To combat COVID-19, the United States Food and Drug Administration issued emergency use authorization in December 2020 for mRNA vaccines developed by Pfizer-BioNTech and Moderna. While the pandemic brought mRNA vaccines into the limelight, melanoma patient Bobby Fentress had experience with mRNA technology nearly a year prior. mRNA vaccines hold promise for fighting infectious diseases beyond the SARS-CoV-2 virus, including fighting cancer. At age 68, Bobby was an early participant in a clinical trial intended to see whether a vaccine made with mRNA could destroy his cancer cells and prevent recurrence.

Bobby’s story began in 2019. He found an odd bump on his middle finger and assumed it was a wart. After his wife urged him to be seen by a dermatologist, he received a call that he would need a biopsy – which ultimately revealed that he had stage 2c melanoma. Several months later, Bobby had most of his middle finger amputated and was told that there was a 50% possibility that the cancer would reoccur.  That’s when Bobby decided to enroll in a clinical trial with HCA Healthcare’s Sarah Cannon Research Institute in Nashville, Tennessee. He received his first shots of a personalized mRNA vaccine created by Moderna in April 2020. These vaccines are developed from a patient’s specific tumor DNA. The DNA of the tumor is analyzed to determine the differences between the tumor and a patient’s own cells and which proteins might elicit the best immune response. The mRNA vaccine is then developed to instruct the body to make these proteins and stimulate an immune response. Patients such as Bobby then receive a series of these vaccine treatments.

“Bobby finished his year of treatment earlier this spring. While it is too early to know if the therapy will work, Bobby’s oncologist, Dr. Meredith McKean, is optimistic.  Immunotherapy has been a game changer for melanoma. With mRNA, the hope is that personalized therapy would offer additional treatment benefit above our standard treatments that we offer for patients broadly. Even for patients like Bobby that had surgery, ten years ago we wouldn’t be able to give him anything but highly toxic therapy options. It’s refreshing to offer a clinical trial like this. While the trial is not yet complete, we have enough data to be hopeful. It’s a very encouraging area that I’m excited about as a provider,” says Dr McKean, associate director of the melanoma and skin cancer research program at Sarah Cannon Research Institute.

https://hcahealthcaretoday.com/

A personalized “cancer vaccine” may help keep a deadly form of skin cancer from growing for years, a small new study in humans suggests. Unlike vaccines that prevent infections, such as measles and influenza, cancer vaccines are a form of immunotherapy that take down cancer cells that already exist. The vaccines train immune cells, called T cells, to better recognize cancer and target it for destruction, while sparing healthy cells in the body. For example, the new experimental vaccine works by training T cells to spot specific proteins on melanoma cells, a type of skin cancer. In the study, scientists found that the T cells continue to “remember” these proteins for at least four years after the vaccination — and they even learn to recognize more melanoma-related proteins over time.

“The only way that could have happened is if there was actually killing of the tumor cells. And presumably it was the T cells induced by the vaccine that did that killing,” said study author Dr. Catherine Wu, a physician-scientist with the Dana-Farber Cancer Institute and Harvard Medical School in Boston and the Broad Institute in Cambridge, Massachusetts. That’s because, once killed, tumor cells fall apart and spill their contents; T cells then swoop in to examine these remains and log that information away for future attacks, Wu said.

While the results are promising, the new study only included eight patients, and more trials need to be conducted to pin down exactly how effective the vaccine is, she added. But as of now, the limited data hint that the vaccine triggers a persistent immune response and can help keep cancer under control, especially when combined with other immunotherapies, the authors noted. The new study, published Jan. 21 in the journal Nature Medicine, included patients with advanced melanoma who had recently undergone surgery for the cancer. The researchers took samples of the patients’ removed tumors and used them to craft personalized vaccines for each of the eight participants.

Source: https://www.realclearscience.com/

There’s another reason to celebrate the gut microbiome—a healthy gut might actually be able to save lives. According to scientists at the Lawson Health Research Institute, all it takes to strengthen your immune system is to improve your gut health, a process that we know is as easy as increasing your ingestion of probiotics and dietary fiber. How’s that for functional food?

These Lawson Health Research Institute scientists are implementing a preliminary study that would discover whether a fecal transplant of a healthy microbiome can help patients with melanoma become more receptive to immunotherapy treatments. During immunotherapy treatments, patients take certain drugs to stimulate their immune systems in order to attack tumors in their bodies. A fecal transplant, according to these researchers, would make their immune systems more receptive to the drugs and, in turn, could help more people successfully fight their cancer.

“We know that some people’s immune systems don’t respond well, and it seems to be associated with the microbes within your gut,” Michael Silverman, M.D., a Lawson associate scientist, said in a video filmed by the research institute. “The goal is to give people healthy microbes to replenish the microbes in their gut so that their immune system responds optimally, and they’re able to control the tumor.”

Source: https://www.mindbodygreen.com/

Researchers at Tel Aviv University have developed a novel nano-vaccine for melanoma, the most aggressive type of skin cancer. Their innovative approach has so far proven effective in preventing the development of melanoma in mouse models and in treating primary tumors and metastases that result from melanoma. The focus of the research is on a nanoparticle that serves as the basis for the new vaccine. The study was led by Prof. Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology and head of the Laboratory for Cancer Research and Nanomedicine at TAU‘s Sackler Faculty of Medicine, and Prof. Helena Florindo of the University of Lisbon while on sabbatical at the Satchi-Fainaro lab at TAU. Melanoma develops in the skin cells that produce melanin or skin pigment.

“The war against cancer in general, and melanoma in particular, has advanced over the years through a variety of treatment modalities, such as chemotherapy, radiation therapy and immunotherapy; but the vaccine approach, which has proven so effective against various viral diseases, has not materialized yet against cancer,” says Prof. Satchi-Fainaro. “In our study, we have shown for the first time that it is possible to produce an effective nano-vaccine against melanoma and to sensitize the immune system to immunotherapies.”

The researchers harnessed tiny particles, about 170 nanometers in size, made of a biodegradable polymer. Within each particle, they “packed“ two peptides — short chains of amino acids, which are expressed in melanoma cells. They then injected the nanoparticles (or “nano-vaccines“) into a mouse model bearing melanoma. “The nanoparticles acted just like known vaccines for viral-borne diseases,” Prof. Satchi-Fainaro explains. “They stimulated the immune system of the mice, and the immune cells learned to identify and attack cells containing the two peptides — that is, the melanoma cells. This meant that, from now on, the immune system of the immunized mice will attack melanoma cells if and when they appear in the body.”

The results were published recently in Nature Nanotechnology.

Source: https://english.tau.ac.il/

Immunotherapy’s promise in the fight against cancer drew international attention after two scientists won a Nobel Prize this year for unleashing the ability of the immune system to eliminate tumor cells.

But their approach, which keeps cancer cells from shutting off the immune system’s powerful T-cells before they can fight tumors, is just one way to use the body’s natural defenses against deadly disease. A team of Vanderbilt University bioengineers today announced a major breakthrough in another: penetrating tumor-infiltrating immune cells and flipping on a switch that tells them to start fighting. The team designed a nanoscale particle to do that and found early success using it on human melanoma tissue.

“Tumors are pretty conniving and have evolved many ways to evade detection from our immune system,” said John T. Wilson, assistant professor of chemical and biomolecular engineering and biomedical engineering. “Our goal is to rearm the immune system with the tools it needs to destroy cancer cells. “Checkpoint blockade has been a major breakthrough, but despite the huge impact it continues to have, we also know that there are a lot of patients who don’t respond to these therapies. We’ve developed a nanoparticle to find tumors and deliver a specific type of molecule that’s produced naturally by our bodies to fight off cancer.”

That molecule is called cGAMP, and it’s the primary way to switch on what’s known as the stimulator of interferon genes (STING) pathway: a natural mechanism the body uses to mount an immune response that can fight viruses or bacteria or clear out malignant cells. Wilson said his team’s nanoparticle delivers cGAMP in a way that jump-starts the immune response inside the tumor, resulting in the generation of T-cells that can destroy the tumor from the inside and also improve responses to checkpoint blockade.

While the Vanderbilt team’s research focused on melanoma, their work also indicates that this could impact treatment of many cancers, Wilson said, including breast, kidney, head and neck, neuroblastoma, colorectal and lung cancer.

The findings are reported in the journal Nature Nanotechnology.

Source: https://news.vanderbilt.edu/