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/

Scientists from the Terasaki Institute for Biomedical Innovation (TIBI) have developed a contact lens that can capture and detect exosomes, nanometer-sized vesicles found in bodily secretions which have the potential for being diagnostic cancer biomarkers. The lens was designed with microchambers bound to antibodies that can capture exosomes found in tears. This antibody- conjugated signaling microchamber contact lens (ABSM-CL) can be stained for detection with nanoparticle-tagged specific antibodies for selective visualization. This offers a potential platform for cancer pre-screening and a supportive diagnostic tool that is easy, rapid, sensitive, cost-effective, and non-invasive.

Exosomes are formed within most cells and secreted into many bodily fluids, such as plasma, saliva, urine, and tears. Once thought to be the dumping grounds for unwanted materials from their cells of origin, it is now known that exosomes can transport different biomolecules between cells. It has also been shown that there is a wealth of surface proteins on exosomes – some that are common to all exosomes and others that are increased in response to cancer, viral infections, or injury. In addition, exosomes derived from tumors can strongly influence tumor regulation, progression, and metastasis.

Because of these capabilities, there has been much interest in using exosomes for cancer diagnosis and prognosis/treatment prediction. However, this has been hampered by the difficulty in isolating exosomes in sufficient quantity and purity for this purpose. Current methods involve tedious and time-consuming ultracentrifuge and density gradients, lasting at least ten hours to complete.

Source: https://terasaki.org/

Scientists have developed artificial intelligence software that can create proteins that may be useful as vaccines, cancer treatments, or even tools for pulling carbon pollution out of the air. This research was led by the University of Washington School of Medicine and Harvard University.

“The proteins we find in nature are amazing molecules, but designed proteins can do so much more,” said senior author David Baker, a professor of biochemistry at UW Medicine. “In this work, we show that machine learning can be used to design proteins with a wide variety of functions.”

For decades, scientists have used computers to try to engineer proteins. Some proteins, such as antibodies and synthetic binding proteins, have been adapted into medicines to combat COVID-19. Others, such as enzymes, aid in industrial manufacturing. But a single protein molecule often contains thousands of bonded atoms; even with specialized scientific software, they are difficult to study and engineer. Inspired by how machine learning algorithms can generate stories or even images from prompts, the team set out to build similar software for designing new proteins. “The idea is the same: neural networks can be trained to see patterns in data. Once trained, you can give it a prompt and see if it can generate an elegant solution. Often the results are compelling — or even beautiful,” said lead author Joseph Watson, a postdoctoral scholar at UW Medicine.

The team trained multiple neural networks using information from the Protein Data Bank, which is a public repository of hundreds of thousands of protein structures from across all kingdoms of life. The neural networks that resulted have surprised even the scientists who created them.

Deep machine learning program hallucinating new ideas for vaccine molecules

The team developed two approaches for designing proteins with new functions. The first, dubbed “hallucination” is akin to DALL-E or other generative A.I. tools that produce new output based on simple prompts. The second, dubbed “inpainting,” is analogous to the autocomplete feature found in modern search bars and email clients.

“Most people can come up with new images of cats or write a paragraph from a prompt if asked, but with protein design, the human brain cannot do what computers now can,” said lead author Jue Wang, a postdoctoral scholar at UW Medicine. “Humans just cannot imagine what the solution might look like, but we have set up machines that do.”

To explain how the neural networks ‘hallucinate’ a new protein, the team compares it to how it might write a book: “You start with a random assortment of words — total gibberish. Then you impose a requirement such as that in the opening paragraph, it needs to be a dark and stormy night. Then the computer will change the words one at a time and ask itself ‘Does this make my story make more sense?’ If it does, it keeps the changes until a complete story is written,” explains Wang.

Both books and proteins can be understood as long sequences of letters. In the case of proteins, each letter corresponds to a chemical building block called an amino acid. Beginning with a random chain of amino acids, the software mutates the sequence over and over until a final sequence that encodes the desired function is generated. These final amino acid sequences encode proteins that can then be manufactured and studied in the laboratory.

The research is published in the journal Science.

Source: https://newsroom.uw.edu/

During experiments in animal models, researchers at the University of Kansas (KU)  have discovered a possible new approach to immunization against Alzheimer’s disease (AD). Their method uses a recombinant methionine (Met)-rich protein derived from corn that was then oxidized in vitro to produce the antigen: methionine sulfoxide (MetO)-rich protein. This antigen, when injected to the body, goads the immune system into producing antibodies against the MetO component of beta-amyloid, a protein that is toxic to brain cells and seen as a hallmark of Alzheimer’s disease.

“As we age, we have more oxidative stress, and then beta-amyloid and other proteins accumulate and become oxidized and aggregated – these proteins are resistant to degradation or removal,” said lead researcher Jackob Moskovitz, associate professor of pharmacology & toxicology at the KU School of Pharmacy. “In a previous 2011 published study, I injected mouse models of Alzheimer’s disease with a similar methionine sulfoxide-rich protein and showed about 30% reduction of amyloid plaque burden in the hippocampus, the main region where damage from Alzheimer’s disease occurs.”

The MetO-rich protein used by Moskovitz for the vaccination of AD-model mice is able to prompt the immune system to produce antibodies against MetO-containing proteins, including MetO-harboring beta-amyloid. The introduction of the corn-based MetO-rich protein (antigen) fosters the body’s immune system to produce and deploy the antibodies against MetO to previously tolerated MetO-containing proteins (including MetO-beta-amyloid), and ultimately reduce the levels of toxic forms of beta-amyloid and other possible proteins in brain.

According to Moskovitz, there was a roughly 50% improvement in the memory of mice injected with the methionine sulfoxide (MetO)-rich protein versus the control.

The findings have been just published in the peer-reviewed open-access journal Antioxidants.

Source: https://today.ku.edu/

The relentless evolution of the COVID-causing coronavirus has taken a bit of the shine off the vaccines developed during the first year of the pandemic. Versions of the virus that now dominate circulation—Omicron and its subvariants—are more transmissible and adept at evading the body’s immune defenses than its original form. The current shots to the arm can still prevent serious illness, but their ability to ward off infection completely has been diminished. And part of the reason may be the location of the jabs, which some scientists now want to change.

To block infections entirely, scientists want to deliver inoculations to the site where the virus first makes contact: the nose. People could simply spray the vaccines up their nostrils at home, making the preparation much easier to administer. There are eight of these nasal vaccines in clinical development now and three in phase 3 clinical trials, where they are being tested in large groups of people. But making these vaccines has proven to be slow going because of the challenges of creating formulations for this unfamiliar route that are both safe and effective.

What could be most important about nasal vaccines is their ability to awaken a powerful bodily defender known as mucosal immunity, something largely untapped by the standard shots. The mucosal system relies on specialized cells and antibodies within the mucus-rich lining of the nose and other parts of our airways, as well as the gut. These elements move fast and arrive first, stopping the virus, SARS-CoV-2, before it can create a deep infection. “We are dealing with a different threat than we were in 2020,” says Akiko Iwasaki, an immunologist at Yale University. “If we want to contain the spread of the virus, the only way to do that is through mucosal immunity.”

Iwasaki is leading one of several research groups in the U.S. and elsewhere that are working on nasal vaccines. Some of the sprays encapsulate the coronavirus’ spike proteins—the prominent molecule that the virus uses to bind to human cells—into tiny droplets that can be puffed into the sinuses. Others add the gene for the spike to harmless versions of common viruses, such as adenoviruses, and use the defanged virus to deliver the gene into nasal tissue. Still others rely on synthetically bioengineered SARS-CoV-2 converted into a weakened form known as a live attenuated vaccine.

Sourc: https://www.scientificamerican.com/

It sounds like the stuff of science fiction: a man-made crystal that can be attached to antibodies and then supercharge them with potent drugs or imaging agents that can seek out diseased cells with the highest precision, resulting in fewer adverse effects for the patient.

However, that is precisely what researchers from the Australian Centre for Blood Diseases at Monash University in collaboration with the TU Graz (Austria) have developed: the world’s first metal-organic framework (MOFs) antibody-drug delivery system that has the potential to fast-track potent new therapies for cancer, cardiovascular and autoimmune diseases.

Schematic illustration of the new MOF Antibody crystals and their ability to specifically seek out cancer cells to detect them and deliver highly potent drugs with unprecedented precision

The in vitro study showed that when MOF antibody crystals bind to their target cancer cells and if exposed to the low pH in the cells, they break down, delivering the drugs directly and solely to the desired area.

The metal-organic framework, a mixture of metal (zinc) and carbonate ions, and a small organic molecule (an imidazole, a colourless solid compound that is soluble in water) not only keeps the payload attached to the antibody but can also acts as a reservoir of personalised therapeutics. This is a benefit with the potential to become a new medical tool to target specific diseases with customised drugs and optimised doses.

The findings are now published in the world-leading journal Advanced Materials.

Source: https://www.monash.edu/

Using specialized carbon nanotubes, MIT engineers have designed a novel sensor that can detect SARS-CoV-2 without any antibodies, giving a result within minutes. Their new sensor is based on technology that can quickly generate rapid and accurate diagnostics, not just for Covid-19 but for future pandemics, the researchers say.

Using specialized carbon nanotubes, MIT engineers have designed a novel sensor that can detect SARS-CoV-2 without any antibody, giving a result within minutes.

“A rapid test means that you can open up travel much earlier in a future pandemic. You can screen people getting off of an airplane and determine whether they should quarantine or not. You could similarly screen people entering their workplace and so forth,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT and the senior author of the study. “We do not yet have technology that can develop and deploy such sensors fast enough to prevent economic loss.”

The diagnostic is based on carbon nanotube sensor technology that Strano’s lab has previously developed. Once the researchers began working on a Covid-19 sensor, it took them just 10 days to identify a modified carbon nanotube capable of selectively detecting the viral proteins they were looking for, and then test it and incorporate it into a working prototype. This approach also eliminates the need for antibodies or other reagents that are time-consuming to generate, purify, and make widely available.

Several years ago, Strano’s lab developed a novel approach to designing sensors for a variety of molecules. Their technique relies on carbon nanotubes — hollow, nanometer-thick cylinders made of carbon that naturally fluoresce when exposed to laser light. They have shown that by wrapping such tubes in different polymers, they can create sensors that respond to specific target molecules by chemically recognizing them.

Their approach, known as Corona Phase Molecular Recognition (CoPhMoRe), takes advantage of a phenomenon that occurs when certain types of polymers bind to a nanoparticle. Known as amphiphilic polymers, these molecules have hydrophobic regions that latch onto the tubes like anchors and hydrophilic regions that form a series of loops extending away from the tubes.

MIT postdoc Sooyeon Cho and graduate student Xiaojia Jin are the lead authors of the paper, which appears today in Analytical Chemistry. Other authors include MIT graduate students Sungyun Yang and Jianqiao Cui, and postdoc Xun Gong.

Source: https://news.mit.edu/

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 team of scientists has found why elderly people are more susceptible to COVID-19 and are working to reverse the aging process of the body’s immune system.

Scientists from the Technion-Israel Institute of Technology say they have found a way to rejuvenate the aging process of the body’s immune system. Prof. Doron Melamed and doctoral student Reem Dowery sought to understand why the elderly population is more susceptible to severe cases of COVID-19 and why the vaccines seem to be less effective and wane faster among this population. The results of their work were published this month in the peer-reviewed, online medical journal Blood.
The secret begins with B cells, also known as B lymphocytes. These are the cells that produce antibodies against any pathogen that enters the body. They play a key role in protecting people from viruses and diseases.
B cells do not just disappear. They turn into “memory” B cells so that if the body is exposed to a previous pathogen, the individual will not get sick. That is because the immune response will be fast and robust, and it will eliminate the pathogen, often without the individual knowing he or she had been exposed to it.

“Imagine you are growing into adulthood, and you become an adult and then an older person,” Melamed said. “You accumulate in your body many memory cells. You are exposed all the time to pathogens, and hence you make more and more memory cells. Because these are so long-lived, there is no room left for new B cells.”
What happens when a new pathogen, such as the coronavirus, comes along? There are no young B cells that can recognize it. That is one of the reasons why older people are more susceptible to severe COVID-19 and many other diseases. As noted, this happens because of the body’s need for homeostasis, something that Melamed’s lab discovered a decade ago. But this year, they took the discovery another step and figured out a mechanism to override the system.
“We found specific hormonal signals produced by the old B cells, the memory cells, that inhibit the bone marrow from producing new B cells,” Melamed said. “This is a huge discovery. It is like finding a needle in a haystack.”

It also means that, over time, specific drugs or treatments can be found to inhibit one of the hormones in the signaling pathway and get the bone marrow to produce new B cells.

Source: http://www.jpost.com/

A test that spots pancreatic cancer from a single drop of blood could improve survival rates. The first blood test for early diagnosis of the hard-to-spot disease, it could be available within months. Pancreatic cancer has the lowest survival rate of the common cancers, with 7.3 per cent of patients alive five years after diagnosis, compared to 58.4 per cent of bowel cancer patients and 85 per cent of breast cancer patients.

The disease is one of the hardest to diagnose early. This is partly because the pancreas — a pear-shaped gland that makes digestive juices and hormones including insulin — is hidden behind the stomach, making it difficult for tumours to be felt or seen on scans. It also doesn’t usually cause symptoms in the early stages — when they do occur, the signs, such as stomach or back pain, weight loss and indigestion, can be vague and easily confused with conditions, such as irritable bowel syndrome.

Treatments include surgery, radiotherapy and chemotherapy but their effectiveness hinges on early diagnosis. Caught early, before the disease has spread to other organs, up to 25 per cent of patients will live for at least five years. If the disease has spread, average survival is two to six months.

The new test, developed by Swedish biotech firm Immunovia and being trialled on 2,000 people at University College London Hospital, and 20 other centres in the U.S., Spain and Sweden, looks for signs of the disease in patient’s blood. These include different levels of around 30 proteins and other compounds identified by the Swedish scientists.

They provide a distinct chemical fingerprint of the disease. The test picks out the compounds using antibodies that latch on to individual chemicals: sophisticated scanning equipment is then used to measure their levels. Previous research shows the test is 96 per cent accurate in spotting people with early-stage pancreatic cancers.

Source: https://immunovia.com/
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