What if radiation treatments could be given in a handful of seconds rather than weeks of treatments? If surgeons could actually see tumor cells rather than simply hoping they got rid of them all? If scientists could come up with new ways to detect, treat and understand tumors? These were among some of the ideas presented this week in Orlando at the American Association for Cancer Research annual conference, where more than 6,500 scientists shared their work and their hopes for improving the lives of cancer patients. Work against cancer has continued over the last three years, despite the pandemic, said Dr. Robert Vonderheide, the conference’s program committee chair. The thousands of presentations and 20,000-person turnout should convince people of that. Obviously, lots of the research is worth public attention. But with Vonderheide’s guidance, USA TODAY picked three ideas that seemed among the most surprising and hopeful, the kinds of approaches that have the potential to transform cancer treatment and patients’ lives.

The first is “flash” radiation, which concentrates weeks of treatments into a few days; the second, an imaging technology that lights up cancer cells to help surgeons track them down.

“Two of the most fundamental tools, cancer surgery and cancer radiation, are undergoing before our eyes fundamental changes in their technology,” said Vonderheide, who directs the Abramson Cancer Center at the University of Pennsylvania. “They are each promising better success.” A third line of research is providing insights into the role of the nervous system in cancer, which could eventually be used to help patients sleep better, heal faster and live longer. Researchers typically focus on a tumor, but there are “systemic signals that might tell us how best to treat a patient or that a patient actually has a lurking cancer,” Vonderheide said. Like the immune system, which has increasingly been manipulated to help fight cancer over the last decade, the nervous system monitors the body and remembers what it encounters.

“The immune system is probably the first system to know that cancer exists. And probably the nervous system is the next one,” he said. “Maybe there’s new inroads in early detection if we focus on neurological health and immune health.” None of these new approaches is readily available yet, but Vonderheide thinks they’re among the advances worth watching.

At least half of patients with solid tumors endure radiation at some point during their treatment. Radiation typically takes about 15 minutes, though sessions can last an hour or more and are scheduled every weekday for three to nine weeks – requiring a total of 15 to 40 visits. Patients may suffer skin burns, dry mouth, difficulties eating and swallowing, and exhaustion. They must upend their lives and often a loved one’s to get to a clinic so many times.

Radiation therapy is traditionally delivered in small doses over weeks so it can efficiently kills tumor cells while being less toxic to surrounding healthy tissue, said Constantinos Koumenis, a professor of radiation biology at the University of Pennsylvania‘s Perelman School of Medicine. But as many radiation patients can attest, treatments still do plenty of damage to normal tissue. Instead, Koumenis and dozens of other research teams have been testing “flash radiation,” which uses ultra high dose rate beams of energy to zap tumor cells. Patients might get the same amount of radiation in just two to four sessions of less than 1 second each. “The vulnerability of the tumor cells is essentially the same,” Koumenis said. “What’s different is the normal tissue is more resistant to the flash radiation.”

Source: https://eu.usatoday.com/

 BioNtech (22UAy.DE) has dosed the first patient with its BNT163 herpes vaccine candidate designed to prevent genital lesions as part of a first-in-human Phase 1 clinical research study, the German vaccine maker said on Wednesday.

The vaccine candidate is meant to prevent HSV-2, the herpes simplex virus that causes genital herpes, and potentially HSV-1, which causes oral herpes and can lead to genital herpes.

Source: https://www.reuters.com/

A shapeshifting robotic microswarm may one day act as a toothbrush, rinse, and dental floss in one. The technology, developed by a multidisciplinary team at the University of Pennsylvania, is poised to offer a new and automated way to perform the mundane but critical daily tasks of brushing and flossing. It’s a system that could be particularly valuable for those who lack the manual dexterity to clean their teeth effectively themselves.

The building blocks of these microrobots are iron oxide nanoparticles that have both catalytic and magnetic activity. Using a magnetic field, researchers could direct their motion and configuration to form either bristlelike structures that sweep away dental plaque from the broad surfaces of teeth, or elongated strings that can slip between teeth like a length of floss. In both instances, a catalytic reaction drives the nanoparticles to produce antimicrobials that kill harmful oral bacteria on site.

Experiments using this system on mock and real human teeth showed that the robotic assemblies can conform to a variety of shapes to nearly eliminate the sticky biofilms that lead to cavities and gum disease. 

“Routine oral care is cumbersome and can pose challenges for many people, especially those who have hard time cleaning their teeth” says Hyun (Michel) Koo, a professor in the Department of Orthodontics  in Penn’s School of Dental Medicine and co-corresponding author on the study. “You have to brush your teeth, then floss your teeth, then rinse your mouth; it’s a manual, multistep process. The big innovation here is that the robotics system can do all three in a single, hands-free, automated way.”

“Nanoparticles can be shaped and controlled with magnetic fields in surprising ways,” says Edward Steager, a senior research investigator in Penn’s School of Engineering and Applied Science and co-corresponding author. “We form bristles that can extend, sweep, and even transfer back and forth across a space, much like flossing. The way it works is similar to how a robotic arm might reach out and clean a surface. The system can be programmed to do the nanoparticle assembly and motion control automatically.”

The Penn team shared their findings establishing a proof-of-concept for the robotic system in the journal ACS Nano.

Source: https://penntoday.upenn.edu/

In 2010, three patients received an experimental form of immunotherapy for leukemia through a clinical trial at the University of Pennsylvania. Two of the patients went into complete remission—and stayed that way.  The treatment, known as CAR T-cell therapy, is now FDA-approved to treat certain blood cancers. It involves engineering a patient’s own white blood cells to attack cancerous cells and then returning them to the body. Since clinical trials and FDA approval, CAR T-cell therapy has already been used to successfully treat and clear certain cancers. However, CAR T-cell therapy doesn’t lead to lasting remissions for every patient, and it can cause serious side effects. A new report offers clues about why the treatment is sometimes remarkably effective.

The two patients who responded well to CAR T-cell therapy in 2010 remained disease free for over a decade. One of the men, a Californian named Doug Olson, is now 75. The other, William Ludwig, died early last year of COVID-19. Researchers were able to detect CAR T-cells lingering in Olson and Ludwig’s bloodstreams long after their cancers disappeared, although the types of immune cells that persisted were slightly different than anticipated, the team reported in Nature.

Two T-cells (red) attack an oral squamous cancer cell (white)—a fight that’s part of the natural immune response. Clinical researchers are developing a new type of therapy that modifies a patient’s T-cells to better attack cancer

“Now we can finally say the word ‘cure’ with CAR T-cells,” Carl June, the principal investigator for the University of Pennsylvania trial, told The New York Times.

Olson and Ludwig were among the earliest recipients of CAR T-cell therapy, allowing clinicians a chance to track the patients’ cells and condition over the past decade. “To use the word ‘cure,’ you really need a long time to follow up to make sure people don’t relapse,” says David Maloney, the medical director of cellular immunotherapy at the Immunotherapy Integrated Research Center at the Fred Hutchinson Cancer Research Center in Seattle. “When we get these people out to 10 and 11 years post-treatment, that encourages us to be a little more forceful in saying that perhaps patients are cured in some cases.”

Source: https://www.popsci.com/

Combining technologies that proved hugely successful against cancer and in COVID-19 vaccines, researchers at the University of Pennsylvania have shown they can effectively treat a leading cause of heart disease. For now the success has only been achieved in mice, but the milestone offers hope for millions of people whose heart muscle is damaged by scar tissue. There is no effective treatment for this fibrosis, which leads to heart disease, the leading cause of death in the United States, said Dr. Jonathan Epstein, a Penn professor of cardiovascular research who helped lead the new work, published in the journal Science.

In his new research, Epstein reversed fibrosis by re-engineering cells, as has been done with a successful blood cancer treatment called CAR-T. In this case, however, the treatment took place inside the body rather than in a lab dish. The team delivered the treatment using mRNA technology, which has been proven over the last year with hundreds of millions of people receiving mRNA-based COVID vaccines.

“If it works (in people), it really could have enormous impact,” Epstein said. “Almost every type of heart disease is accompanied by fibrosis.”

About 50% of heart failure is directly caused by this scar tissue, which prevents the heart from relaxing and pumping effectively. Fibrosis also is involved in leading causes of lung and kidney disease.

Source: https://eu.usatoday.com

The development of the Pfizer-BioNTech coronavirus vaccine, the first approved jab in the West, is the crowning achievement of decades of work for Hungarian biochemist Katalin Kariko, who fled to the US from communist rule in the 1980s.

When trials found the Pfizer-BioNTech coronavirus vaccine to be safe and 95 percent effective in November, it was the crowning achievement of Katalin Kariko’s 40 years of research on the genetic code RNA (ribonucleic acid). Her first reaction was a sense of “redemption,” Kariko told The Daily Telegraph.

“I was grabbing the air, I got so excited I was afraid that I might die or something,” she said from her home in Philadelphia. “When I am knocked down I know how to pick myself up, but I always enjoyed working… I imagined all of the diseases I could treat.”

Born in January 1955 in a Christian family in the town of Szolnok in central Hungary – a year before the doomed heroism of the uprising against the Soviet-backed communist regime – Kariko grew up in nearby Kisujszellas on the Great Hungarian Plain, where her father was a butcher. Fascinated by science from a young age, Kariko began her career at the age of 23 at the University of Szeged’s Biological Research Centre, where she obtained her PhD.

It was there that she first developed her interest in RNA. But communist Hungary’s laboratories lacked resources, and in 1985 the university sacked her. Consequently, Kariko looked for work abroad, getting a job at Temple University in Philadelphia the same year. Hungarians were forbidden from taking money out of the country, so she sold the family car and hid the proceeds in her 2-year-old daughter’s teddy bear. “It was a one-way ticket,” she told Business Insider. “We didn’t know anybody.”

Not everything went as planned after Kariko’s escape from communism. At the end of the 1980s, the scientific community was focused on DNA, which was seen as the key to understanding how to develop treatments for diseases such as cancer. But Kariko’s main interest was RNA, the genetic code that gives cells instructions on how to make proteins.

At the time, research into RNA attracted criticism because the body’s immune system sees it as an intruder, meaning that it often provokes strong inflammatory reactions. In 1995, Kariko was about to be made a professor at the University of Pennsylvania, but instead she was consigned to the rank of researcher.

“Usually, at that point, people just say goodbye and leave because it’s so horrible,” Kariko told medical publication Stat. She went through a cancer scare at the time, while her husband was stuck in Hungary trying to sort out visa issues. “I tried to imagine: Everything is here, and I just have to do better experiments,” she continued. Kariko was also on the receiving end of sexism, with colleagues asking her the name of her supervisor when she was running her own lab.

Kariko persisted in the face of these difficulties. “From outside, it seemed crazy, struggling, but I was happy in the lab,” she told Business Insider. “My husband always, even today, says, ‘This is entertainment for you.’ I don’t say that I go to work. It is like play.” Thanks to Kariko’s position at the University of Pennsylvania, she was able to send her daughter Susan Francia there for a quarter of the tuition costs. Francia won gold on the US rowing team in the 2008 and 2012 Olympics.

It was a serendipitous meeting in front of a photocopier in 1997 that turbocharged Kariko’s career. She met immunologist Drew Weissman, who was working on an HIV vaccine. They decided to collaborate to develop a way of allowing synthetic RNA to go unrecognised by the body’s immune system – an endeavour that succeeded to widespread acclaim in 2005. The duo continued their research and succeeded in placing RNA in lipid nanoparticles, a coating that prevents them from degrading too quickly and facilitates their entry into cells.

The researchers behind the Pfizer-BioNTech and Moderna jabs used these techniques to develop their vaccines.

Source: https://www.france24.com/

In 1959, former Cornell physicist Richard Feynman delivered his famous lecture “There’s Plenty of Room at the Bottom,” in which he described the opportunity for shrinking technology, from machines to computer chips, to incredibly small sizes. Well, the bottom just got more crowded. A Cornell-led collaboration has created the first microscopic robots that incorporate semiconductor components, allowing them to be controlled – and made to walk – with standard electronic signals. These robots, roughly the size of paramecium, provide a template for building even more complex versions that utilize silicon-based intelligence, can be mass produced, and may someday travel through human tissue and blood.

The collaboration is led by Itai Cohen, professor of physics, Paul McEuen, the John A. Newman Professor of Physical Science – both in the College of Arts and Sciences – and their former postdoctoral researcher Marc Miskin, who is now an assistant professor at the University of Pennsylvania.

The walking robots are the latest iteration, and in many ways an evolution, of Cohen and McEuen’s previous nanoscale creations, from microscopic sensors to graphene-based origami machines. The new robots are about 5 microns thick (a micron is one-millionth of a meter), 40 microns wide and range from 40 to 70 microns in length. Each bot consists of a simple circuit made from silicon photovoltaics – which essentially functions as the torso and brain – and four electrochemical actuators that function as legs. As basic as the tiny machines may seem, creating the legs was an enormous feat.

“In the context of the robot’s brains, there’s a sense in which we’re just taking existing semiconductor technology and making it small and releasable,” said McEuen, who co-chairs the Nanoscale Science and Microsystems Engineering (NEXT Nano) Task Force, part of the provost’s Radical Collaboration initiative, and directs the Kavli Institute at Cornell for Nanoscale Science.

“But the legs did not exist before,” McEuen said. “There were no small, electrically activatable actuators that you could use. So we had to invent those and then combine them with the electronics.”

The team’s paper, “Electronically Integrated, Mass-Manufactured, Microscopic Robots,” has been published  in Nature.

Source: https://news.cornell.edu/
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https://thenextweb.com/

For the first time in the United States, a gene editing tool has been used to treat advanced cancer in three patients and showed promising early results in a pilot phase 1 clinical trial. So far the treatment appears safe, and more results are expected soon. To develop a safer and more effective treatment for cancer patients, scientists from the University of Pennsylvania, the Parker Institute for Cancer Immunotherapy in San Francisco and Tmunity Therapeutics, a biotech company in Philadelphia, developed an advanced version of immunotherapy. In this treatment, a patient’s own immune cells are removed from the body, trained to recognize specific cancer cells and then finally injected back into the patient where they multiply and destroy them.

Unlike chemotherapy or radiation therapy, which directly kills cancer cells, immunotherapy activates the body’s own immune system to do the work. This team used a gene editing tool called CRISPR to alter immune cells, turning them into trained soldiers to locate and kill cancer cells. By using this technique, the team hoped to develop a more effective form of immunotherapy with minimal side effects.

Better CRISPR-based gene editors for the diagnosis and treatment of cancer and other disorders, . combining chemistry, biology and nanotechnology, are used to engineer, control and deliver gene editing tools more efficiently and precisely.

The first step in making these tumor-killing cells used in the cancer drug trial was to isolate the T-cells – a type of white blood cells that fights pathogens and cancer cells – from the blood of the cancer patients. Two patients with advanced multiple myeloma and one patient with myxoid/round cell liposarcomav were enrolled for this study.

To arm the T-cells and bolster their tumor-fighting skills without harming normal cells, scientists genetically engineered the T-cells – disabling three genes and adding one gene – before returning them to the patients.

The first two of these deleted genes encode T-cell receptors, which are proteins found on the surface of the T-cells that can recognize and bind specific molecules, known as antigens, on cancer cells. When these engineered T-cells bind to these antigens, it allows them to attack and directly kill the cancer cells. But the problem is that a single T-cell can recognize multiple different antigens in the body, making them less focused on finding the cancer cells. By eliminating these two genes, the T-cells are less likely to attack the wrong target or the host, a phenomenon called autoimmunity, In addition, they disrupted a third gene, called programmed cell death protein 1, which slows down the immune response. Disabling the programmed cell death protein 1 gene improves the efficiency of T-cells.

The final step in the transformation of these cells was adding a gene which produces a new T-cell receptor that recognizes and grabs onto a specific marker on the cancer cells called NY-ESO-1. With three genes deleted and one added, the T-cells are now ready to fight cancer.

Source: https://theconversation.com/

While it is well known within the medical community that there is a link between the bacteria Helicobacter pylori (H pylori) and rates of gastric cancer—commonly referred to as stomach cancer—the rates and risk among Americans has been largely understudied. Now, after analyzing records of close to 400,000 patients, researchers in the Perelman School of Medicine, University of Pennsylvania, have found that successfully eliminating H pylori from the gastrointestinal tract led to a 75 percent reduction in the risk of gastric cancer. Researchers also found that rates of gastric cancer after detection of H pylori infection are higher among specific populations, suggesting that people who fall into these groups could benefit from more careful monitoring. The study is published in the journal Gastroenterology. H pylori is estimated to infect half of the world’s population, largely those in the eastern parts of the world. It can cause ulcers and other gastrointestinal issues but does not cause issues in the majority of people, and so many people are unaware they have it.

3D illustration of Helicobacter pylori, bacterium which causes gastric and duodenal ulcer

“The problem was that all research out of the U.S. used to study gastric cancer and determine American’s risk of developing it did not take into account H pylori infection, and studies worldwide have shown this infection is actually the leading risk factor for this type of cancer,” says the study’s lead author Shria Kumar, a fellow in the division of Gastroenterology.

The research team found that African American, Asian, Hispanic and Latin, American Indian, and Inuit Americans have a significantly higher risk of H pylori infection and of developing gastric cancer. Risks, when compared to the general population, are also higher among men, those who smoke, and among those whose H pylori infection is detected at an older age.

Source: https://penntoday.upenn.edu/