Ultrasound guides supercharged immune cells to only attack cancer

Bioengineers at the University of California San Diego have developed a cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue. The new experimental therapy significantly slowed down the growth of solid cancerous tumors in mice. The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering.

The work addresses a longstanding problem in the field of cancer immunotherapy: how to make chimeric antigen receptor (CAR) T-cell therapy safe and effective at treating solid tumors. CAR T-cell therapy is a promising new approach to treat cancer. It involves collecting a patient’s T cells and genetically engineering them to express special receptors, called CAR, on their surface that recognize specific antigens on cancer cells. The resulting CAR T cells are then infused back into the patient to find and attack cells that have the cancer antigens on their surface.

This therapy has worked well for the treatment of some blood cancers and lymphoma, but not against solid tumors. That’s because many of the target antigens on these tumors are also expressed on normal tissues and organs. This can cause toxic side effects that can kills cells—these effects are known as on-target, off-tumor toxicity.

CAR T cells are so potent that they may also attack normal tissues that are expressing the target antigens at low levels,” said first author Yiqian (Shirley) Wu, a project scientist in Wang’s lab.

The problem with standard CAR T cells is that they are always on—they are always expressing the CAR protein, so you cannot control their activation,” explained Wu.

To combat this issue, the team took standard CAR T cells and re-engineered them so that they only express the CAR protein when ultrasound energy is applied. This allowed the researchers to choose where and when the genes of CAR T cells get switched on.

We use ultrasound to successfully control CAR T cells directly in vivo for cancer immunotherapy,” said Wang, who is a faculty member of the Institute of Engineering in Medicine and the Center for Nano-ImmunoEngineering, both at UC San Diego. What’s exciting about the use of ultrasound, noted Wang, is that it can penetrate tens of centimeters beneath the skin, so this type of therapy has the potential to non-invasively treat tumors that are buried deep inside the body.

The team’s approach involves injecting the re-engineered CAR T cells into tumors in mice and then placing a small ultrasound transducer on an area of the skin that’s on top of the tumor to activate the CAR T cells. The transducer uses what’s called focused ultrasound beams to focus or concentrate short pulses of ultrasound energy at the tumor. This causes the tumor to heat up moderately—in this case, to a temperature of 43 degrees Celsius (109 degrees Fahrenheit)—without affecting the surrounding tissue. The CAR T cells in this study are equipped with a gene that produces the CAR protein only when exposed to heat. As a result, the CAR T cells only switch on where ultrasound is applied.

The research was published in the journal Nature Biomedical Engineering.

Ultrasound Therapy for Alzheimer’s

One promising possibility when it comes to treating Alzheimer’s is the idea of using non-invasive ultrasound to take out toxic brain plaques, and a group of researchers in Australia have been at the cutting edge of this technology for a number of years. The scientists’ latest investigations have uncovered some surprising new ways this technique can improve cognition in mouse models of the disease, which they believe could have wider implications for restoring cognition in the elderly.

Led by Professor Jürgen Götz at the University of Queensland, the researchers behind this promising ultrasound therapy published some exciting early results in 2015. Initially, the idea was to use ultrasound in combination with gas-filled microbubbles to temporarily open the blood-brain barrier to allow in drugs that take out toxic amyloid and tau brain plaques that destroy synapses and are seen as key drivers of Alzheimer’s disease.

As it turned out, this technique proved an effective way to clear away the brain plaques without the need for any drugs, with the ultrasound activating microglial cells that could digest the plaques all on their own. The scientists then published a study in 2018 demonstrating how this technique could safely clear the toxic brain plaques and restore memory function in mouse models resembling human brains of 80 to 90 years old, and set their sights on human trials.

As they’ve continued to study this technique in mice, the scientists have continued to uncover new information about its effects on the brain, and how it might boost cognition. In newly published research, the team carried out new experiments on mouse models of brains with age-related deterioration, and found that it brought about yet further unexpected changes.

One of the physiological hallmarks of age-related cognitive decline is a deterioration in a type of signaling between neurons called long-term potentiation (LTP), which is associated with memory. The scientists were able to show that combining ultrasound with the microbubbles fully restored LTP in one region of the hippocampus. More interesting still, the ultrasound proved even more effective without the help of the microbubbles, not only restoring LTP but also improving the spatial learning deficits of the elderly mice by improving synaptic signaling and neurogenesis, among other physiological alterations.

Ultrasound may be a way to not just tackle brain plaques associated with Alzheimer’s, but also age-related cognitive decline in the broader population

The team’s ultrasound technique could serve as a two-pronged attack on Alzheimer’s, combining with microbubbles and plaque-busting agents to tackle the condition while simultaneously improving cognition via a separate pathway. And promisingly, the scientists believe the technique may one day prove a viable way to address age-related cognitive decline in the broader population.

Historically, we have been using ultrasound together with small gas-filled bubbles to open the almost-impenetrable blood-brain barrier and get therapeutics from the bloodstream into the brain,” Professor Götz says. “The entire research team was surprised by the remarkable restoration in cognition. We conclude therapeutic ultrasound is a non-invasive way to enhance cognition in the elderly.”

Source: https://qbi.uq.edu.au/

Ultrasound Can Selectively Kill Cancer Cells

A new technique could offer a targeted approach to fighting cancer: low-intensity pulses of ultrasound have been shown to selectively kill cancer cells while leaving normal cells unharmed.

Ultrasound wavessound waves with frequencies higher than humans can hear—have been used as a cancer treatment before, albeit in a broad-brush approach: high-intensity bursts of ultrasound can heat up tissue, killing cancer and normal cells in a target area. Now, scientists and engineers are exploring the use of low-intensity pulsed ultrasound (LIPUS) in an effort to create a more selective treatment.

A study describing the effectiveness of the new approach in cell models was published in Applied Physics Letters. The researchers behind the work caution that it is still preliminary—it still has not been tested in a live animal let alone in a human, and there remain several key challenges to address—but the results so far are promising.

The research began five years ago when Caltech‘s Michael Ortiz, Frank and Ora Lee Marble Professor of Aeronautics and Mechanical Engineering, found himself pondering whether the physical differences between cancer cells and healthy cells—things like size, cell-wall thickness, and size of the organelles within them—might affect how they vibrate when bombarded with sound waves and how the vibrations might trigger cancer cell death.

I have my moments of inspiration,” Ortiz says wryly.

And so Ortiz built a mathematical model to see how cells would react to different frequencies and pulses of sound waves. Together with then-graduate student Stefanie Heyden (PhD ’14), who is now at ETH Zurich, Ortiz published a paper in 2016 in the Journal of the Mechanics and Physics of Solids showing that there was a gap in the so-called resonant growth rates of cancerous and healthy cells. That gap meant that a carefully tuned sound wave could, in theory, cause the cell membranes of cancerous cells to vibrate to the point that they ruptured while leaving healthy cells unharmed. Ortiz dubbed the process “oncotripsy” from the Greek oncos (for tumor) and tripsy (for breaking).

Source: https://www.caltech.edu/

Microwave Stimulated Nanoparticles To Fight Efficiently Cancer

A physicist at The University of Texas at Arlington (UTA) has proposed a new concept for treating cancer cells. In a recently published paper in the journal Nanomedicine: Nanotechnology, Biology and Medicine, UTA physics Professor Wei Chen and a team of international collaborators advanced the idea of using titanium dioxide (TiO2) nanoparticles stimulated by microwaves to trigger the death of cancer cells without damaging the normal cells around them.

The method is called microwave-induced radical therapy, which the team refers to as microdynamic therapy, or MDT. The use of TiO2 nanoparticles activated by light and ultrasound in cancer treatments has been studied extensively, but this marks the first time researchers have shown that the nanoparticles can be effectively activated by microwaves for cancer cell destruction—potentially opening new doors to treatment for patients fighting the disease. Chen said the new therapy centers on reactive oxygen species, or ROS, which are a natural byproduct of the body’s metabolism of oxygen. ROS help kill toxins in the body, but can also be damaging to cells if they reach a critical level. TiO2 enters cells and produces ROS, which are able to damage plasma membranes, mitochondria and DNA, causing cell death.

Cancer cells are characterized by a higher steady-state saturation of ROS than normal, healthy cells,” Chen said. “This new therapy allows us to exploit that by raising the saturation of ROS in cancer cells to a critical level that triggers cell death without pushing the normal cells to that same threshold.

The pilot study for this new treatment concept builds upon Chen’s expertise in the use of nanoparticles to combat cancer.

Chen’s collaborators hail from the Guangdong Academy of Medical Sciences and Beihang University. The team conducted experiments that demonstrate the nanoparticles can significantly suppress the growth of osteosarcomas under microwave irradiation.

While TiO2 and low-power microwave irradiation alone did not effectively kill cancer cells, the combination of the two proved successful in creating a toxic effect for the tumor cells. Microwave ablation therapy has already proven to be an effective treatment against bone cancer, obtaining better results than MDT. However, MDT has applications for combatting other types of cancer, not just the osteosarcomas used for this pilot case.

Using light to activate ROS—as is seen in photodynamic therapy—can be challenging for the treatment of tumors deeply located within the body; in contrast, microwaves lend the ability to create deeper penetration that propagates through all types of tissues and non-metallic materials.

This new discovery is exciting because it potentially creates new avenues for treating cancer patients without causing debilitating side effects,” Chen said. “This targeted, localized method allows us to keep healthy cells intact so patients are better equipped to battle the disease.

Source: https://www.uta.edu/

Soldiers To Control Machines With Their Minds

The Department of Defense’s research and development wing, DARPA, is working on technology to read and write to the human brain. The focus isn’t on mind control but rather machine control, allowing the human brain to directly send instructions to machines. The goal of the process is to streamline thought control of machines to the point where humans could control them with a simple helmet or head-mounted device, making operating such systems easier.

The brain makes physical events happen by turning thoughts into action, sending instructions through the nervous system to organs, limbs, and other parts of the body. It effortlessly sends out a constant stream of commands to do everything from drive a car to make breakfast. To operate today’s machines, humans being need a middleman of sorts, a physical control system manipulated by hands, fingers, and feet.

What if human beings could cut out the middleman, operating a machine simply by thinking at it? So DARPA is funding the (Next Generation Nonsurgical Neurotechnology  (N3) initiative. N3’s goal is to create a control system for machines—including weapons—that can directly interact with the human brain. According to IEEE Spectrum, DARPA is experimenting with “magnetic fields, electric fields, acoustic fields (ultrasound) and light” as a means of controlling machines.

The implications of such a technology are huge. Instead of designing complicated controls and control systems for every machine or weapon devised, engineers could instead just create a thought-operated control system. Wearable technology becomes easier to operate as it doesn’t require a separate control system. This could also apply to notifications and data: as IEEE Spectrum points out, network administrators could feel intrusions into computer networks. DAPRA is, of course, an arm of the Pentagon, and a neurotechnological interface would almost certainly find its way into weapons.

DARPA has awarded development contracts to six groups for amounts of up to $19.48 million each. Each group has one year to prove their ability to read and write to brain tissue with an 18-month animal testing period to follow.

Source: https://www.popularmechanics.com/

Ultrasonic Comb Kills Lice

The Israeli company ParaSonic is developing a revolutionary home-use ultrasonic device that kills lice and their eggs in a single 5-minute combing treatmentHead lice infestations are a global problem, with 12 million infestations in children and adults every year in the United States alone. It can be very difficult to completely eradicate head lice, and re-infection occurs easily.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

ParaSonic’s revolutionary home-use comb, XlicerTM kills lice and their eggs in a single combing treatment that takes about 5 minutes. Ultrasound waves generated by the teeth of the wide-toothed comb destroy lice and lice eggs after exposure of about one second. XlicerTM simultaneously sprays a natural solution onto the hair, to augment the efficacy of the the ultrasound and significantly increase the lice and eggs’ mortality. Because there is no use of pesticides, there is no possibility of the lice developing resistance. The comb’s wide-tooth design means no discomfort to the person being treated.

Source: http://para-sonic.com/