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Towards Universal Cancer Immunotherapy

Scientists at ETH Zurich in Switzerland have made a breakthrough towards designing an off-the-shelf treatment for immunotherapy against cancer. A synthetic protein tweak can allow immune cells from any donor to be given to any patient without the risk of a dangerous immune reaction. Cancer patients might one day benefit from being administered immune cells from healthy donors. But as things stand, receiving donor cells can cause severe or even fatal immune reactions. A researcher at ETH Zurich has now developed a technology that avoids these.

Edo Kapetanovic is a medical doctor, but for a while now he has devoted himself entirely to research in synthetic immunology. He has completed his doctoral studies in immunoengineering and is working at the Department of Biosystems Science and Engineering at ETH Zurich in Basel. His big goal is to develop new cancer therapies by providing patients with immune cells derived from donor blood. He is now getting closer to this goal: he has managed to modify donor cells so that they attack only the tumour cells and not patient’s healthy cells. The technology has been tested in the lab in human cells, but it will take more time and development before the patients can benefit from the technology.

Administering donor cells is far from straightforward: the immune system is specialised in distinguishing foreign molecules from ‘self’ and will attack any foreign cell. This is particularly dangerous for immunocompromised patients, as donor cells can recognize patient cells as foreign and trigger a violent and, consequently, fatal immune response in the recipient, known as a graft-versus-host reaction. That is why today’s immunotherapeutic treatments for cancer mainly use a patient’s own immune cells rather than donated cells.

Kapetanovic and his team have now succeeded in engineering immune cells that are safe of graft-versus-host reaction. Generally speaking, approved immunotherapies for cancer take one of two approaches, and both depend on cells known as killer cells, mostly killer T cells. In one approach, experts extract the patient’s own killer cells and modify them in the lab so that they specifically recognise and eliminate cancer cells. These modified cells are then administered to the patient.

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Artificial Intelligence Develops Cancer Treatment in Just 30 Days

In less than a month, researchers have used AlphaFold, an artificial intelligence (AI)-powered protein structure database, to design and synthesize a potential drug to treat hepatocellular carcinoma (HCC), the most common type of primary liver cancer. The researchers successfully applied AlphaFold to an end-to-end AI-powered drug discovery platform called Pharma.AI. That included a biocomputational engine, PandaOmics, and a generative chemistry engine, Chemistry42. They discovered a novel target for HCC – a previously undiscovered treatment pathway – and developed a “novel hit molecule” that could bind to that target without the aid of an experimentally determined structure. The feat was accomplished in just 30 days from target selection and after only synthesizing seven compounds.

In a second round of AI-powered compound generation, researchers discovered a more potent hit molecule – although any potential drug would still need to undergo clinical trials. The study – published in Chemical Science – is led by the University of Toronto Acceleration Consortium Director Alán Aspuru-Guzik, Nobel laureate Michael Levitt and Insilico Medicine founder and CEO Alex Zhavoronkov.

While the world was fascinated with advances in generative AI in art and language, our generative AI algorithms managed to design potent inhibitors of a target with an AlphaFold-derived structure,” Zhavoronkov said. “AlphaFold broke new scientific ground in predicting the structure of all proteins in the human body,” added co-author Feng Ren, chief scientific officer and co-CEO of Insilico Medicine. “At Insilico Medicine, we saw that as an incredible opportunity to take these structures and apply them to our end-to-end AI platform in order to generate novel therapeutics to tackle diseases with high unmet need. This paper is an important first step in that direction.”

Source: https://www.utoronto.ca/
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https://www.dailymail.co.uk/

Jaw-dropping GPT-4 makes ChatGPT Obsolete

In the first day after it was unveiled, GPT-4 stunned many users in early tests and a company demo with its ability to draft lawsuits, pass standardized exams and build a working website from a hand-drawn sketch.

On Tuesday, OpenAI announced the next-generation version of the artificial intelligence technology that underpins its viral chatbot tool, ChatGPT. The more powerful GPT-4 promises to blow previous iterations out of the water, potentially changing the way we use the internet to work, play and create. But it could also add to challenging questions around how AI tools can upend professions, enable students to cheat, and shift our relationship with technology.

GPT-4 is an updated version of the company’s large language model, which is trained on vast amounts of online data to generate complex responses to user prompts. It is now available via a waitlist and has already made its way into some third-party products, including Microsoft’s new AI-powered Bing search engine. Some users with early access to the tool are sharing their experiences and highlighting some of its most compelling use cases.

https://edition.cnn.com/

 

Cancer Fighting Protein Kills Tumors and Boosts the Body’s Immunity

Tumor cells typically alter their energy metabolism and increase glucose uptake to support their rapid division and spread. This limits glucose availability for immune cells and therefore dampens the body’s anti-cancer immune responseBy searching for proteins that both regulate the metabolism of cancer cells and affect immune cells in tumors, a team led by investigators at Massachusetts General Hospital (MGH) recently identified a potential target for therapies that could simultaneously drain tumors of energy and boost the immune response against them.

For the research, which is published in Cancer Discovery, Keith T. Flaherty, MD, the director of Clinical Research at the MGH Cancer Center and a professor of medicine at Harvard Medical School, and his colleagues developed a new computational tool called BipotentR that can identify targets that block immune activation and also stimulate a second user-defined pathway (in this case, metabolism). When applied to gene expression data from patients with cancer who were treated with immunotherapy, as well as from cell lines and animal models, the tool identified 38 cancer cellspecific immune-metabolic regulators.

Artificial intelligence techniques showed that the activity level of these regulators in tumors predicted patients’ outcomes after receiving immunotherapyThe topmost identified regulator, ESRRA (Estrogen Related Receptor Alpha), was activated in immunotherapy-resistant tumors of many types. Inhibiting ESRAA killed tumors by suppressing energy metabolism and activating two immune mechanisms involving different types of immune cells.The scientists also demonstrated that BipotentR can be applied to other survival mechanisms used by cancer cells, such as their ability to promote blood vessel formation to increase their blood supply. Therefore, BipotentR, available at http://bipotentr.dfci.harvard.edu, provides a resource for discovering single drugs that can act through one cancer-related pathway while simultaneously stimulating an immune response.

Source: https://www.massgeneral.org/
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https://www.thebrighterside.news/

Blood Test Predicts Alzeimer’s Pathology Up to 10 Years Before Symptoms

A new blood test may be able to detect Alzheimer’s disease-related pathology up to 10 years before symptoms appear, according to a press release from Durin Technologies.

Our test correctly identified nearly 97% of participants who were diagnosed as cognitively normal at the time their samples were taken, but who progressed, within an average of 48 months, to either the mild cognitive impairment stage or more advanced Alzheimer’s disease,” Cassandra DeMarshall, PhD, Durin Technologies director, said in a press release. “To our knowledge, this is the first blood test to accurately detect Alzheimer’s-related pathology several years before either clinical symptoms or more expensive and invasive tests can identify the disease.”

The minimally invasive test was developed through a collaboration between researchers at Durin Technologies, a biotechnology company, and Rowan-Virtua School of Osteopathic Medicine (SOM) in Stratford, New Jersey. Researchers evaluated 328 blood samples, with 106 samples from participants without dementia for comparison. Samples were analyzed for eight autoantibody biomarkers, according to the release.

“An accurate, noninvasive blood test for early detection and monitoring of AD could bend the curve of clinical outcomes through earlier participation in clinical trials and monitoring of AD progression of patients under treatment,” Robert Nagele, PhD, Durin’s founder and chief scientific officer and professor of geriatrics and gerontology at Rowan-Virtua SOM, said in the release.

Source: https://www.durintechnologies.com/ 
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https://www.healio.com/

How to Suck up Carbon Pollution

Scientists have set out a way to suck planet-heating carbon pollution from the air, turn it into sodium bicarbonate and store it in oceans, according to a new paper. The technique could be up to three times more efficient than current carbon capture technology, say the authors of the study, published Wednesday in the journal Science Advances.

Tackling the climate crisis means drastically reducing the burning of fossil fuels, which releases planet-heating pollution. But because humans have already pumped so much of this pollution into the atmosphere and are unlikely to sufficiently reduce emissions in the near term, scientists say we also need to remove it from the airNature does this – forests and oceans, for example, are valuable carbon sinks – but not quickly enough to keep pace with the amounts humans are producing. So we have turned to technology.

One method is to capture carbon pollution directly at the source, for example from steel or cement plants. But another way, which this study focuses on, is “direct air capture.” This involves sucking carbon pollution directly out of the atmosphere and then storing it, often by injecting it into the ground. The problem with direct air capture is that while carbon dioxide may be a very potent planet-heating gas, its concentrations are very small – it makes up about 0.04% of air. This means removing it directly from the air is challenging and expensive.

“It’s a “significant hurdle,” Arup SenGupta, a professor at Lehigh University and a study author. Even the biggest facilities can only remove relatively small amounts and it costs several hundred dollars to remove each ton of carbonClimeworks’ direct air removal project in Iceland is the largest facility, according to the company, and can capture up to 4,000 tons of carbon dioxide a year. That’s equivalent to the carbon pollution produced by fewer than 800 cars over a year. The new technique laid out in the study can help tackle those problems, said SenGupta. The team have used copper to modify the absorbent material used in direct air capture. The result is an absorbent “which can remove CO2 from the atmosphere at ultra-dilute concentration at a capacity which is two to three times greater than existing absorbents,” SenGupta said. This material can be produced easily and cheaply and would help drive down the costs of direct air capture, he added. Once the carbon dioxide is captured, it can then be turned into sodium bicarbonatebaking soda – using seawater and released into the ocean at a small concentration.

The oceansare infinite sinks,” SenGupta explained. “If you put all the CO2 from the atmosphere, emitted every day – or every year – into the ocean, the increase in concentration would be very, very minor.” Gupta’s idea is that direct air capture plants can be located offshore, giving them access to abundant amounts of seawater for the process.

Source: https://www.science.org/
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https://edition.cnn.com/

New Superconducting Material For Levitating High-Speed Train or to Achieve Nuclear Fusion

In a historic achievement, University of Rochester researchers have created a superconducting material at both a temperature and pressure low enough for practical applications.

With this material, the dawn of ambient superconductivity and applied technologies has arrived,” according to a team led by Ranga Dias, an assistant professor of mechanical engineering and of physics. In a paper in Nature, the researchers describe a nitrogen-doped lutetium hydride (NDLH) that exhibits superconductivity at 69 degrees Fahrenheit (26 degrees Celsius) and 10 kilobars (145,000 pounds per square inch, or psi) of pressure.

Although 145,000 psi might still seem extraordinarily high (pressure at sea level is about 15 psi), strain engineering techniques routinely used in chip manufacturing, for example, incorporate materials held together by internal chemical pressures that are even higher.

Scientists have been pursuing this breakthrough in condensed matter physics for more than a century. Superconducting materials have two key properties: electrical resistance vanishes, and the magnetic fields that are expelled pass around the superconducting material. Such materials could enable:

  • Power grids that transmit electricity without the loss of up to 200 million megawatt hours (MWh) of the energy that now occurs due to resistance in the wires
  • Frictionless, levitating high-speed trains
  • More affordable medical imaging and scanning techniques such as MRI and magnetocardiography
  • Faster, more efficient electronics for digital logic and memory device technology
  • Tokamak machines that use magnetic fields to confine plasmas to achieve fusion as a source of unlimited power

Previously, the Dias team reported creating two materialscarbonaceous sulfur hydride and yttrium superhydride—that are superconducting at 58 degrees Fahrenheit (14,4 degrees Celsius) /39 million psi and 12 degrees Fahreneheit/26 million psi respectively, in papers in Nature and Physical Review Letters.

Source: https://www.rochester.edu/

New Discovery Could Help to Stop Alzheimer’s

Nearly two dozen experimental therapies targeting the immune system are in clinical trials for Alzheimer’s disease, a reflection of the growing recognition that immune processes play a key role in driving the brain damage that leads to confusion, memory loss and other debilitating symptoms.

Many of the immunity-focused Alzheimer’s drugs under development are aimed at microglia, the brain’s resident immune cells, which can injure brain tissue if they’re activated at the wrong time or in the wrong way. A new study from researchers at Washington University School of Medicine in St. Louis indicates that microglia partner with another type of immune cellT cells — to cause neurodegeneration. Studying mice with Alzheimer’s-like damage in their brains due to the protein tau, the researchers discovered that microglia attract powerful cell-killing T cells into the brain, and that most of the neurodegeneration could be avoided by blocking the T cells’ entry or activation. The findings, published March 8 in the journal Nature, suggest that targeting T cells is an alternative route to preventing neurodegeneration and treating Alzheimer’s disease and related diseases involving tau, collectively known as tauopathies.

This could really change the way we think about developing treatments for Alzheimer’s disease and related conditions,” said senior author David M. Holtzman, MD, Professor of Neurology. “Before this study, we knew that T cells were increased in the brains of people with Alzheimer’s disease and other tauopathies, but we didn’t know for sure that they caused neurodegeneration. These findings open up exciting new therapeutic approaches. Some widely used drugs target T cells. Fingolomid, for example, is commonly used to treat multiple sclerosis, which is an autoimmune disease of the brain and spinal cord. It’s likely that some drugs that act on T cells could be moved into clinical trials for Alzheimer’s disease and other tauopathies if these drugs are protective in animal models.”

Source: https://medicine.wustl.edu

Same-Sex Couples Could Have a Biological Child Together in the Future

Scientists have created mice with two biological fathers by generating eggs from male cells, a development that opens up radical new possibilities for reproduction. The advance could ultimately pave the way for treatments for severe forms of infertility, as well as raising the tantalising prospect of same-sex couples being able to have a biological child together in the future.

This is the first case of making robust mammal oocytes from male cells,” said Katsuhiko Hayashi, who led the work at Kyushu University in Japan and is internationally renowned as a pioneer in the field of lab-grown eggs and sperm.

Hayashi, who presented the development at the Third International Summit on Human Genome Editing at the Francis Crick Institute in London on Wednesday, predicts that it will be technically possible to create a viable human egg from a male skin cell within a decade. Others suggested this timeline was optimistic given that scientists are yet to create viable lab-grown human eggs from female cells. Previously scientists have created mice that technically had two biological fathers through a chain of elaborate steps, including genetic engineering. However, this is the first time viable eggs have been cultivated from male cells and marks a significant advance. Hayashi’s team is now attempting to replicate this achievement with human cells, although there would be significant hurdles for the use of lab-grown eggs for clinical purposes, including establishing their safety.

Purely in terms of technology, it will be possible [in humans] even in 10 years,” he said, adding that he personally would be in favour of the technology being used clinically to allow two men to have a baby if it were shown to be safe. “I don’t know whether they’ll be available for reproduction,” he said. “That is not a question just for the scientific programme, but also for [society].”

The technique could also be applied to treat severe forms of infertility, including women with Turner’s syndrome, in whom one copy of the X chromosome is missing or partly missing, and Hayashi said this application was the primary motivation for the research. “Creating lab-grown gametes from human cells was more challenging than for mouse cells,” said Prof George Daley, the dean of Harvard Medical School. “We still don’t understand enough of the unique biology of human gametogenesis to reproduce Hayashi’s provocative work in mice.”

Source: https://www.theguardian.com/

VUITY Only FDA-Approved Eye Drop to Treat Presbyopia is Now Available

Allergan, an AbbVie (NYSE: ABBV) company, today announced that VUITY (pilocarpine HCl ophthalmic solution) 1.25%, the first and only eye drop approved by the U.S. Food and Drug Administration (FDA) to treat presbyopia, is now available by prescription in pharmacies nationwide. Presbyopia, or age-related blurry near vision, can be diagnosed through a basic eye exam by an eye doctor (optometrist or ophthalmologist) and is a common and progressive eye condition that affects 128 million Americans, or nearly half of the U.S. adult population.


We are pleased to be able to bring this first-of-its-kind treatment to market sooner than expected for the millions of Americans with presbyopia who may benefit from it,” said Jag Dosanjh, senior vice president medical therapeutics, Allergan, an AbbVie company. “This significant innovation in age-related eye health reflects our commitment to advance vision care and expands our leading portfolio of treatments for eye care providers and their patients.”

Many Americans deal with presbyopia, which typically begins around age 40, by relying on reading glasses or resorting to work-arounds like zooming in on their digital devices to see up close. As an optometrist who also has presbyopia, I’m personally and professionally excited to try VUITY for myself, as well as offer it to my patients with age-related blurry near vision,” said optometrist Dr. Selina McGee, Fellow of the American Academy of Optometry. “With VUITY now available, it is a good time for those who experience age-related blurry near vision to visit their eye doctor for an exam and to discuss their options to manage this common condition.

Source: https://news.abbvie.com/