March 28, 2023
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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/
Categories: Uncategorized
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Tags: antibodies, antigens, cancer, cells, colorectal cancer, Dendritic cells, drugs, Food and Drug Administration, immune response, melanoma, Moderna, mRNA, NCI, pancreatic cancer, Pfizer-BioNTech, proteins, SARS-CoV-2 virus, spike protein, T-cells, tumor, tumors, vaccines, Vrije Universiteit Brussel
February 16, 2023
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At 82 years old, with an aggressive form of blood cancer that six courses of chemotherapy had failed to eliminate, “Paul” appeared to be out of options. With each long and unpleasant round of treatment, his doctors had been working their way down a list of common cancer drugs, hoping to hit on something that would prove effective—and crossing them off one by one. The usual cancer killers were not doing their job.
With nothing to lose, Paul’s doctors enrolled him in a trial set up by the Medical University of Vienna in Austria, where he lives. The university was testing a new matchmaking technology developed by a UK-based company called Exscientia that pairs individual patients with the precise drugs they need, taking into account the subtle biological differences between people.
The researchers took a small sample of tissue from Paul (his real name is not known because his identity was obscured in the trial). They divided the sample, which included both normal cells and cancer cells, into more than a hundred pieces and exposed them to various cocktails of drugs. Then, using robotic automation and computer vision (machine-learning models trained to identify small changes in cells), they watched to see what would happen. In effect, the researchers were doing what the doctors had done: trying different drugs to see what worked. But instead of putting a patient through multiple months-long courses of chemotherapy, they were testing dozens of treatments all at the same time.
The approach allowed the team to carry out an exhaustive search for the right drug. Some of the medicines didn’t kill Paul’s cancer cells. Others harmed his healthy cells. Paul was too frail to take the drug that came out on top. So he was given the runner-up in the matchmaking process: a cancer drug marketed by the pharma giant Johnson & Johnson that Paul’s doctors had not tried because previous trials had suggested it was not effective at treating his type of cancer.
It worked. Two years on, Paul was in complete remission—his cancer was gone. The approach is a big change for the treatment of cancer, says Exscientia’s CEO, Andrew Hopkins: “The technology we have to test drugs in the clinic really does translate to real patients.”
Source: https://www.technologyreview.com/
Categories: Uncategorized
| Tags: AI, Artificial Intelligence, cancer cells, cells, chemotherapy, complete remission, drugs, Exscientia, Johnson & Johnson, machine-learning, matchmaking technology, Medical University of Vienna, robotic automation, tissue
January 6, 2023
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Scientists at Brigham and Women’s Hospital (BWH) have found a way to fight cancer with cancer. The team genetically engineered cancer cells to release anti-cancer drugs at the site of established tumors, as well as stimulating the immune system against the disease. Tests in mice proved promising as both a therapy and a preventative vaccine.
Cancer vaccines are an emerging area of research, where patients are often administered inactive tumor cells or proteins expressed at high levels by cancer cells. This trains the immune system to recognize existing tumors and mount an assault on them, and can prevent the spread or appearance of new tumors. For the new study, the BWH team took a new approach, using living tumor cells instead.
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| Tags: Brigham and Women's Hospital, BWH, cancer, cancer vaccines, CRISPR, drugs, Glioblastoma, immune system, inactive tumor cells, living tumor cells, metastatic cancer, proteins, therapeutic tumor cells, ThTC, tumors, vaccine
November 28, 2022
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With the help of an AI, researchers at Chalmers University of Technology, Sweden, have succeeded in designing synthetic DNA that controls the cells’ protein production. The technology can contribute to the development and production of vaccines, drugs for severe diseases, as well as alternative food proteins much faster and at significantly lower costs than today.
How our genes are expressed is a process that is fundamental to the functionality of cells in all living organisms. Simply put, the genetic code in DNA is transcribed to the molecule messenger RNA (mRNA), which tells the cell’s factory which protein to produce and in which quantities.
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| Tags: AI, cancer, cell, cell's protein, cell’s factory, Chalmers University of Technology, COVID-19, DNA, drugs, food proteins, gene expression, genes, genetic code, immune system, mRNA, mRNA vaccine, protein, protein-based drugs, RNA, severe diseases, synthetic DNA, vaccines, virus
October 5, 2022
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A simple eye test that predicts death from cardiovascular disease has been developed by British scientists. It combines artificial intelligence (AI) with scans of the retina – a membrane at the back of peepers that contains light sensitive cells. The technique could lead to a screening programme – enabling drugs and lifestyle changes to be prescribed decades before symptoms emerge. Lead author Professor Alicja Regina Rudnicka, of St George’s University of London, said the test is inexpensive, accessible and non-invasive. People at risk of stroke, heart attack and other circulatory conditions could undergo RV (artificial intelligence enabled retinal vasculometry) during routine visits to the optician.
Prof Rudnicka said: “It has the potential for reaching a higher proportion of the population in the community because of ‘high street’ availability. “RV offers an alternative predictive biomarker to traditional risk-scores for vascular health – without the need for blood sampling or blood pressure measurement. “It is highly likely to help prolong disease-free status in an ever-aging population with increasing comorbidities, and assist with minimising healthcare costs associated with lifelong vascular diseases.”
An algorithm called QUARTZ was developed based on retinal images from tens of thousands of Britons aged 40 to 69. It focused on the width, area and curvature, or tortuosity, of tiny blood vessels called arterioles and venules. The performance of QUARTZ was compared with the widely used Framingham Risk Scores framework – both separately and jointly.
The health of all the participants was tracked for an average of seven to nine years, during which time there were 327 and 201 circulatory disease deaths among 64,144 UK Biobank and 5,862 EPIC-Norfolk participants respectively. In men, arteriolar and venular width, tortuosity, and width variation emerged as important predictors of death from circulatory disease. In women, arteriolar and venular area and width and venular tortuosity and width variation contributed to risk prediction.
The predictive impact of retinal vasculature on circulatory disease death interacted with smoking, drugs to treat high blood pressure, and previous heart attacks. Overall, these predictive models, based on age, smoking, medical history and retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk.
Source: https://www.mirror.co.uk/
Categories: Uncategorized
| Tags: : Blood vessels, AI, algorithm, arterioles, Artificial Intelligence, Biobank, blood pressure, cardiovascular disease, death, drugs, eye test, Framingham Risk Scores, heart attack, light-sensitive cells, QUARTZ, retina, retinal vasculature, retinal vasculometry, RV, smoking, St George's University of London, stroke, venules
July 1, 2022
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A Northwestern University-led team of investigators has developed a small, soft, flexible implant that relieves pain on demand and without the use of drugs. Described in a study published in Science, the first-of-its-kind device could provide a much-needed alternative to opioids and other highly addictive medications.
The biocompatible, water-soluble device works by softly wrapping around nerves to deliver precise, targeted cooling, which numbs nerves and blocks pain signals to the brain. An external pump enables the user to remotely activate the device and then increase or decrease its intensity. After the device is no longer needed, it naturally absorbs into the body — bypassing the need for surgical extraction.
The scientists believe the device will be most valuable for patients who undergo routine surgeries or even amputations that commonly require post-operative medications. Surgeons could implant the device during the procedure to help manage the patient’s post-operative pain.
A Northwestern University-led team has developed a small, pain-relieving implant that could provide a much-needed alternative to opioids and other highly addictive medications.
“Although opioids are extremely effective, they also are extremely addictive,” said John Rogers, PhD, Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery, who led the device’s development. Jonathan Reeder, former postdoctoral fellow in the Rogers laboratory, is the paper’s first author.
“As engineers, we are motivated by the idea of treating pain without drugs — in ways that can be turned on and off instantly, with user control over the intensity of relief,” said Rogers, who is also the founding director of the Querrey Simpson Institute for Bioelectronics. “The technology reported here exploits the mechanism that causes your fingers to feel number when cold. Our implant allows that effect to be produced in a programmable way, directly and locally to targeted nerves, even those deep within surrounding soft tissues.”
While other cooling therapies and nerve blockers have been tested experimentally, all have limitations that the new device overcomes. Previously, scientists have explored cryotherapies, for example, which are injected with a needle. Instead of targeting specific nerves, these imprecise approaches cool large areas of tissue, potentially leading to unwanted effects such as tissue damage and inflammation.
At its widest point, the tiny device is just five millimeters wide. One end is curled into a cuff that softly wraps around a single nerve, bypassing the need for sutures. By precisely targeting only the affected nerve, the device spares surrounding regions from unnecessary cooling, which could lead to side effects.
“You don’t want to inadvertently cool other nerves or the tissues that are unrelated to the nerve transmitting the painful stimuli,” MacEwan said. “We want to block the pain signals, not the nerves that control motor function and enable you to use your hand, for example.”
Source: https://news.feinberg.northwestern.edu/
Categories: Uncategorized
| Tags: brain, drugs, Electrical Stimulation, implant, nerve blockers, nerves, Northwestern University, opioids, pain signals, pain-killer, stimuli
March 31, 2022
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Scientists at Caltech have genetically engineered, sound-controlled bacteria that seek and destroy cancer cells. In a new paper appearing in the journal Nature Communications, researchers from the lab of Mikhail Shapiro, professor of chemical engineering and Howard Hughes Medical Institute investigator, show how they have developed a specialized strain of the bacteria Escherichia coli (E. coli) that seeks out and infiltrates cancerous tumors when injected into a patient’s body. Once the bacteria have arrived at their destination, they can be triggered to produce anti-cancer drugs with pulses of ultrasound.
“The goal of this technology is to take advantage of the ability of engineered probiotics to infiltrate tumors, while using ultrasound to activate them to release potent drugs inside the tumor,” Shapiro says.
The starting point for their work was a strain of E. coli called Nissle 1917, which is approved for medical uses in humans. After being injected into the bloodstream, these bacteria spread throughout the body. The patient’s immune system then destroys them—except for those bacteria that have colonized cancerous tumors, which offer an immunosuppressed environment.
To turn the bacteria into a useful tool for treating cancer, the team engineered them to contain two new sets of genes. One set of genes is for producing nanobodies, which are therapeutic proteins that turn off the signals a tumor uses to prevent an anti-tumor response by the immune system. The presence of these nanobodies allow the immune system to attack the tumor. The other set of genes act like a thermal switch for turning the nanobody genes on when the bacteria reaches a specific temperature.
By inserting the temperature-dependent and nanobody genes, the team was able to create strains of bacteria that only produced the tumor-suppressing nanobodies when warmed to a trigger temperature of 42–43 degrees Celsius. Since normal human body temperature is 37 degrees Celsius, these strains do not begin producing their anti-tumor nanobodies when injected into a person. Instead, they quietly grow inside the tumors until an outside source heats them to their trigger temperature.
But how do you heat bacteria that are located in one specific location, potentially deep inside the body where a tumor is growing? For this, the team used focused ultrasound (FUS). FUS is similar to the ultrasound used for imaging internal organs, or a fetus growing in the womb, but has higher intensity and is focused into a tight point. Focusing the ultrasound on one spot causes the tissue in that location to heat up, but not the tissue surrounding it; by controlling the intensity of the ultrasound, the researchers were able to raise the temperature of that tissue to a specific degree.
Source: https://www.caltech.edu/
Categories: Uncategorized
| Tags: bacteria, Caltech, cancer cells, cancerous tumors, drugs, E.coli, escherichia coli, focused ultrasound, FUS, genes, immune system, Nissle 1917, therapeutic proteins, tumor, ultrasound
March 30, 2022
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The biotechnology company Frequency Therapeutics is seeking to reverse hearing loss—not with hearing aids or implants, but with a new kind of regenerative therapy. The company uses small molecules to program progenitor cells, a descendant of stem cells in the inner ear, to create the tiny hair cells that allow us to hear. Hair cells die off when exposed to loud noises or drugs including certain chemotherapies and antibiotics. Frequency’s drug candidate is designed to be injected into the ear to regenerate these cells within the cochlea. In clinical trials, the company has already improved people’s hearing as measured by tests of speech perception—the ability to understand speech and recognize words.
“Speech perception is the No. 1 goal for improving hearing and the No. 1 need we hear from patients,” says Frequency co-founder and Chief Scientific Officer Chris Loose Ph.D.
In Frequency’s first clinical study, the company saw statistically significant improvements in speech perception in some participants after a single injection, with some responses lasting nearly two years. The company has dosed more than 200 patients to date and has seen clinically meaningful improvements in speech perception in three separate clinical studies, with some improvements lasting nearly two years after a single injection. Another study failed to show improvements in hearing compared to the placebo group, but the company attributes that result to flaws in the design of the trial. Now Frequency is recruiting for a 124-person trial from which preliminary results should be available early next year.
The company’s founders, including Loose, MIT Institute Professor Robert Langer, CEO David Lucchino MBA, Senior Vice President Will McLean Ph.D., and Harvard-MIT Health Sciences and Technology affiliate faculty member Jeff Karp, are already gratified to have been able to help people improve their hearing through the clinical trials. They also believe they’re making important contributions toward solving a problem that impacts more than 40 million people in the U.S. and hundreds of millions more around the world.
“Hearing is such an important sense; it connects people to their community and cultivates a sense of identity,” says Karp, who is also a professor of anesthesia at Brigham and Women’s Hospital. “I think the potential to restore hearing will have enormous impact on society.”
Source: https://www.frequencytx.com/
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https://neurosciencenews.com/
Categories: Uncategorized
| Tags: antibiotics, Brigham and Women's Hospital, chemotherapies, cochlea, drugs, Frequency Therapeutics, Hair cells, Harvard-MIT Health Sciences and Technology, hearing loss, implants, MIT, molecules, progenitor cells, regenerative therapy, stem cells
March 18, 2022
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Scientists exploring a novel but highly promising avenue of cancer treatment have developed a type of “invisibility cloak” that helps engineered bacteria sneak through the body’s immune defenses. The result is more powerful delivery of anti-cancer drugs and shrinking of tumors in mice, with the scientists hopeful the approach can overcome toxicity issues that have plagued these techniques so far.
Traditional forms of cancer treatment – radiotherapy, chemotherapy and immunotherapy – each have their own strengths when it comes to combating tumors, and what’s known as therapeutic bacteria could bring its own set of skills into the mix. Bacteria itself can have powerful anti-tumor effects, but genetic engineering could allow it to take on entirely new capabilities, including releasing specific compounds or carrying potent anti-cancer drugs. There are a number of challenges in using bacteria for this purpose, however, with the issue of toxicity chief among them. Living bacteria can grow rapidly in the body, and because the body’s immune system sees them as a threat, too many can trigger an extreme inflammatory response.
”In clinical trials, these toxicities have been shown to be the critical problem, limiting the amount we can dose bacteria and compromising efficacy,” said Columbia University‘s Jaeseung Hahn, who co-led the research. “Some trials had to be terminated due to severe toxicity.”
Addressing this toxicity problem would mean finding (or engineering) bacteria that can evade the body’s immune system and safely make it to a tumor to fulfill their anti-cancer potential. Hahn’s team has made new inroads in this space by turning to sugar polymers called capsular polysaccharides (CAP), which naturally coat bacterial surfaces and protect them from immune attacks.
“We hijacked the CAP system of a probiotic E. coli strain Nissle 1917,” said Tetsuhiro Harimoto, the study’s co-lead author. “With CAP, these bacteria can temporarily evade immune attack; without CAP, they lose their encapsulation protection and can be cleared out in the body. So we decided to try to build an effective on/off switch.”
Source: https://www.engineering.columbia.edu/
Categories: Uncategorized
| Tags: cancer treatment, CAP, capsular polysaccharides, chemotherapy, Columbia University, drugs, engineered bacteria, genetic engineering, immunotherapy, invisibiliyy cloak, radiotherapy, sugar polymers, therapeutic bacteria, TOXICITY, tumors
March 16, 2022
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Senolytics are an emerging class of drugs designed to target zombie-like cells that have stopped dividing and build up in the body as we age, and the past few years have seen some exciting discoveries that demonstrate their potential. Adding another to the list are Mayo Clinic researchers, who have shown that these drugs can protect against aging and its related diseases, by acting on a protein long associated with longevity. The zombie-like cells involved in this research are known as senescent cells, and their accumulation during aging is associated with a range of diseases. Recent studies have shown that using senolytics to clear them out could serve as new and effective treatments for dementia and diabetes, and also improve health and lifespan more broadly.
The Mayo Clinic team were exploring how senolytics can influence levels of a protein called a-klotho, known to help protect older people from the effects of aging. The role of this protein in the aging process is well established and has placed it at the center of much research in this space, with studies demonstrating how it could help reverse osteoarthritis and regenerate old muscles. Levels of a-klotho are also known to decrease with age, and studies have shown these declines shorten the lifespan of mice. Conversely, inserting genes that encode for the protein has been shown to increase the lifespan of mice by 30 percent. Boosting its levels in humans has been problematic, however, as its larger size would require it to be administered intravenously. But now the Mayo Clinic scientists believe they have found another route, as senolytic drugs can be administered orally.
They first showed that senescent cells reduce levels of a-klotho in human cells. They then demonstrated that using a combination of senolytic drugs on three different types of mice could counter this and increase levels of a-klotho. This effect was then observed in follow-up experiments on patients with idiopathic pulmonary fibrosis, a lung disease that can cause breathing difficulty, frailty and death.
“We show that there is an avenue for an orally active, small-molecule approach to increase this beneficial protein and also to amplify the action of senolytic drugs,” says James Kirkland, M.D., Ph.D., a Mayo Clinic internist and senior author of the study.
Source: https://www.thelancet.com/
Categories: Uncategorized
| Tags: a-klotho, ageing, aging, dementia, diabetes, drugs, genes, longevity, Mayo Clinic, Osteoarthritis, protein, senescent cell, senolytics, zombie-like cells
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