Transhumanismus

Dubbed “living drugs,” CAR T cells are bioengineered from a patient’s own immune cells to make them better able to hunt and destroy cancer.

The treatment is successfully tackling previously untreatable blood cancers. Six therapies are already approved by the FDA. Over a thousand clinical trials are underway. These aren’t limited to cancer—they cover a range of difficult medical problems such as autoimmune diseases, heart conditions, and viral infections including HIV. They may even slow down the biological processes that contribute to aging.

But CAR T has an Achilles heel.

Once injected into the body, the cells often slowly dwindle. Called “exhaustion,” this process erodes therapeutic effect over time and has dire medical consequences. According to Dr. Evan Weber at the University of Pennsylvania, more than 50 percent of people who respond to CAR T therapies eventually relapse. This may also be why CAR T cells have struggled to fight off solid tumors in breast, pancreatic, or deadly brain cancers.

This month, two teams found a potential solution—make CAR T cells more like stem cells. Known for their regenerative abilities, stem cells easily repopulate the body. Both teams identified the same protein “master switch” to make engineered cells resemble stem cells.

One study, led by Weber, found that adding the protein, called FOXO1, revved up metabolism and health in CAR T cells in mice. Another study from a team at the Peter MacCallum Cancer Center in Australia found FOXO1-boosted cells appeared genetically similar to immune stem cells and were better able to fend off solid tumors.

While still early, “these findings may help improve the design of CAR T cell therapies and potentially benefit a wider range of patients,” said Weber in a press release.

Here’s how CAR T cell therapy usually works.

The approach focuses on T cells, a particular type of immune cell that naturally hunts downs and eliminates infections and cancers inside the body. Enemy cells are dotted with a specific set of proteins, a kind of cellular fingerprint, that T cells recognize and latch onto.

Tumors also have a unique signature. But they can be sneaky, with some eventually developing ways to evade immune surveillance. In solid cancers, for example, they can pump out chemicals that fight off immune cell defenders, allowing the cancer to grow and spread.

CAR T cells are designed to override these barriers.

To make them, medical practitioners remove T cells from the body and genetically engineer them to produce tailormade protein hooks targeting a particular protein on tumor cells. The supercharged T cells are then grown in petri dishes and transfused back into the body.

In the beginning, CAR T was a last-resort blood cancer treatment, but now it’s a first-line therapy. Keeping the engineered cells around inside the body, however, has been a struggle. With time, the cells stop dividing and become dysfunctional, potentially allowing the cancer to relapse.

To tackle cell exhaustion, Weber’s team found inspiration in the body itself.

Our immune system has a cellular ledger tracking previous infections. The cells making up this ledger are called memory T cells. They’re a formidable military reserve, a portion of which resemble stem cells. When the immune system detects an invader it’s seen before—a virus, bacteria, or cancer cell—these reserve cells rapidly proliferate to fend off the attack.

CAR T cells don’t usually have this ability. Inside multiple cancers, they eventually die off—allowing cancers to return. Why?

In 2012, Dr. Crystal Mackall at Stanford University found several changes in gene expression that lead to CAR T cell exhaustion. In the new study, together with Weber, the team discovered a protein, FOXO1, that could lengthen CAR T’s effects.

In one test, a drug that inhibited FOXO1 caused CAR T cells to rapidly fail and eventually die in petri dishes. Erasing genes encoding FOXO1 also hindered the cells and increased signs of CAR T exhaustion. When infused into mice with leukemia, CAR T cells without FOXO1 couldn’t treat the cancer. By contrast, increasing levels of FOXO1 helped the cells readily fight it off.

Analyzing genes related to FOXO1, the team found they were mostly connected to immune cell memory. It’s likely that adding the gene encoding FOXO1 to CAR T cells promotes a stable memory for the cells, so they can easily recognize potential harm—be it cancer or pathogen—long after the initial infection.

When treating mice with leukemia, a single dose of the FOXO1-enhanced cells decreased cancer growth and increased survival up to five-fold compared to standard CAR T therapy. The enhanced treatment also tackled a type of bone cancer in mice, which is often hard to treat without surgery and chemotherapy.

Meanwhile, the Australian team also zeroed in on FOXO1. Led by Drs. Junyun Lai, Paul Beavis, and Phillip Darcy, the team was looking for protein candidates to enhance CAR T longevity.

The idea was, like their natural counterparts, engineered CAR T cells also need a healthy metabolism to thrive and divide.

They started by analyzing a protein previously shown to enhance CAR T metabolism, potentially lowering the chances of exhaustion. Mapping the epigenome and transcriptome in CAR T cells—both of which tell us how genes are expressed—they also discovered FOXO1 regulating CAR T cell longevity.

As a proof of concept, the team induced exhaustion in the engineered cells by increasingly restricting their ability to divide.

In mice with cancer, cells supercharged with FOXO1 lasted longer by months than those that hadn’t been boosted. The critters’ liver and kidney functions remained normal, and they didn’t lose weight during the treatment, a marker of overall health. The FOXO1 boost also changed how genes were expressed in the cells—they looked younger, as if in a stem cell-like state.

The new recipe also worked in T cells donated by six people with cancer who had undergone standard CAR T therapy. Adding a dose of FOXO1 to these cells increased their metabolism.

Multiple CAR T clinical trials are ongoing. But “the effects of such cells are transient and do not provide long-term protection against exhaustion,” wrote Darcy and team. In other words, durability is key for CAR T cells to live up to their full potential.

A FOXO1 boost offers a way—although it may not be the only way.

“By studying factors that drive memory in T cells, like FOXO1, we can enhance our understanding of why CAR T cells persist and work more effectively in some patients compared to others,” said Weber.

Image Credit: Gerardo Sotillo, Stanford Medicine

Tired: Listening to music.
Wired: Feeling the music.

A mind-bending new suit straps onto your torso, ankles and wrists, then uses actuators to translate audio into vivid vibration. The result: a new way for everyone to experience music, according to its creators. That’s especially exciting for people who have trouble hearing.

The Music: Not Impossible suit was created by design firm Not Impossible Labs and electronics manufacturing company Avnet. The suit can create sensations to go with pre-recorded music, or a “Vibrotactile DJ” can adjust the sensations in real time during a live music event.”

Billboard writer Andy Hermann tried the suit out, and it sounds like a trip.

“Sure enough, a pulse timed to a kickdrum throbs into my ankles and up through my legs,” he wrote. “Gradually, [the DJ] brings in other elements: the tap of a woodblock in my wrists, a bass line massaging my lower back, a harp tickling a melody across my chest.”

To show the suit off, Not Impossible and Avnet organized a performance this past weekend by the band Greta Van Fleet at the Life is Beautiful Festival in Las Vegas. The company allowed attendees to don the suits. Mandy Harvey, a deaf musician who stole the show on America’s Got Talent last year, talked about what the performance meant to her in a video Avnet posted to Facebook.

“It was an unbelievable experience to have an entire audience group who are all experiencing the same thing at the same time,” she said. “For being a deaf person, showing up at a concert, that never happens. You’re always excluded.”

READ MORE: Not Impossible Labs, Zappos Hope to Make Concerts More Accessible for the Deaf — and Cooler for Everyone [Billboard]

More on accessible design: New Tech Allows Deaf People To Sense Sounds

The post Make Music A Full Body Experience With A “Vibro-Tactile” Suit appeared first on Futurism.

Today’s prosthetics can give people with missing limbs the ability to do almost anything — run marathons, climb mountains, you name it. But when it comes to letting those people feel what they could with a natural limb, the devices, however mechanically sophisticated, invariably fall short.

Now researchers have created a “synthetic skin” with a sense of touch that not only matches the sensitivity of natural skin, but in some cases even exceeds it. Now the only challenge is getting that information back into the wearer’s nervous system.

When something presses against your skin, your nerves receive and transmit that pressure to the brain in the form of electrical signals.

To mimic that biological process, the researchers suspended a flexible polymer, dusted with magnetic particles, over a magnetic sensor. The effect is like a drum: Applying even the tiniest amount of pressure to the membrane causes the magnetic particles to move closer to the sensors, and they transmit this movement electronically.

The research, which could open the door to super-sensitive prosthetics, was published Wednesday in the journal Science Robotics.

Tests shows that the skin can sense extremely subtle pressure, such as a blowing breeze, dripping water, or crawling ants. In some cases, the synthetic skin responded to pressures so gentle that natural human skin wouldn’t be able to detect them.

While the sensing ability of this synthetic skin is remarkable, the team’s research doesn’t address how to transmit the signals to the human brain. Other scientists are working on that, though, so eventually this synthetic skin could give prosthetic wearers the ability to feel forces even their biological-limbed friends can’t detect.

READ MORE: A Skin-Inspired Tactile Sensor for Smart Prosthetics [Science Robotics]

More on synthetic skin: Electronic Skin Lets Amputees Feel Pain Through Their Prosthetics

The post “Synthetic Skin” Could Give Prosthesis Users a Superhuman Sense of Touch appeared first on Futurism.

There’s a gadget that some say can help alleviate depression and enhance creativity. All you have to do is place a pair of electrodes on your scalp and the device will deliver electrical current to your brain. It’s readily available on Amazon or you can even make your own.

But in a new paper published this week in the Creativity Research Journal, psychologists at Georgetown University warned that the practice is spreading before we have a good understanding of its health effects, especially since consumers are already buying and building unregulated devices to shock them. They also cautioned that the technique, which scientists call transcranial electrical stimulation (tES), could have adverse effects on the brains of young people.

“There are multiple potential concerns with DIY-ers self-administering electric current to their brains, but this use of tES may be inevitable,” said co-author Adam Green in a press release. “And, certainly, anytime there is risk of harm with a technology, the scariest risks are those associated with kids and the developing brain”

Yes, there’s evidence that tES can help patients with depression, anxiety, Parkinson’s disease, and other serious conditions, the Georgetown researchers acknowledge.

But that’s only when it’s administered by a trained health care provider. When administering tES at home, people might ignore safety directions, they wrote, or their home-brewed devices could deliver unsafe amounts of current. And because it’s not yet clear what effects of tES might be on the still-developing brains of young people, the psychologists advise teachers and parents to resist the temptation to use the devices to encourage creativity among children.

The takeaway: tES is likely here to stay, and it may provide real benefits. But for everyone’s sake, consumer-oriented tES devices should be regulated to protect users.

READ MORE: Use of electrical brain stimulation to foster creativity has sweeping implications [Eurekalert]

More on transcranial electrical stimulation: DARPA’s New Brain Device Increases Learning Speed by 40%

The post People Are Zapping Their Brains to Boost Creativity. Experts Have Concerns. appeared first on Futurism.

The military is making it easier than ever for soldiers to distance themselves from the consequences of war. When drone warfare emerged, pilots could, for the first time, sit in an office in the U.S. and drop bombs in the Middle East.

Now, one pilot can do it all, just using their mind — no hands required.

Earlier this month, DARPA, the military’s research division, unveiled a project that it had been working on since 2015: technology that grants one person the ability to pilot multiple planes and drones with their mind.

“As of today, signals from the brain can be used to command and control … not just one aircraft but three simultaneous types of aircraft,” Justin Sanchez, director of DARPA’s Biological Technologies Office, said, according to Defense One.

Sanchez may have unveiled this research effort at a “Trajectory of Neurotechnology” session at DARPA’s 60th anniversary event, but his team has been making steady progress for years. Back in 2016, a volunteer equipped with a brain-computer interface (BCI) was able to pilot an aircraft in a flight simulator while keeping two other planes in formation — all using just his thoughts, a spokesperson from DARPA’s Biological Technologies Office told Futurism.

In 2017, Copeland was able to steer a plane through another simulation, this time receiving haptic feedback — if the plane needed to be steered in a certain direction, Copeland’s neural implant would create a tingling sensation in his hands.

There’s a catch. The DARPA spokesperson told Futurism that because this BCI makes use of electrodes implanted in and on the brain’s sensory and motor cortices, experimentation has been limited to volunteers with varying degrees of paralysis. That is: the people steering these simulated planes already had brain electrodes, or at least already had reason to undergo surgery.

To try and figure out how to make this technology more accessible and not require surgical placement of a metal probe into people’s brains, DARPA recently launched the NExt-Generation Nonsurgical Neurotechnology (N3) program. The plan is to make a device with similar capabilities, but it’ll look more like an EEG cap that the pilot can take off once a mission is done.

“The envisioned N3 system would be a tool that the user could wield for the duration of a task or mission, then put aside,” said Al Emondi, head of N3, according to the spokesperson. “I don’t like comparisons to a joystick or keyboard because they don’t reflect the full potential of N3 technology, but they’re useful for conveying the basic notion of an interface with computers.”

READ MORE: It’s Now Possible To Telepathically Communicate with a Drone Swarm [Defense One]

More on DARPA research: DARPA Is Funding Research Into AI That Can Explain What It’s “Thinking”

The post Military Pilots Can Control Three Jets at Once via a Neural Implant appeared first on Futurism.

Today, about 10 people on Earth have bladders they weren’t born with. No, they didn’t receive bladder transplants — doctors grew these folks new bladders using the recipients’ own cells.

On Tuesday, the BBC published a report on the still-nascent procedure of transplanting lab-grown bladders. In it, the publication talks to Luke Massella, who underwent the procedure more than a decade ago. Massella was born with spina bifida, which carries with it a risk of damage to the bladder and urinary tract. Now, he lives a normal life, he told the BBC.

“I was kind of facing the possibility I might have to do dialysis [blood purification via machine] for the rest of my life,” he said. “I wouldn’t be able to play sports, and have the normal kid life with my brother.”

All that changed after Anthony Atala, a surgeon at Boston Children’s Hospital, decided he was going to grow a new bladder for Massella.

To do that, Atala first removed a small piece of Massella’s own bladder. He then removed cells from this portion of bladder and multiplied them in a petri dish. Once he had enough cells, he coated a scaffold with the cells and placed the whole thing in a temperature controlled, high oxygen environment. After a few weeks, the lab-created bladder was ready for transplantation into Massella.

“So it was pretty much like getting a bladder transplant, but from my own cells, so you don’t have to deal with rejection,” said Massella.

The number of people with lab-grown bladders might still be low enough to count on your fingers, but researchers are making huge advances in growing everything from organs to skin in the lab. Eventually, we might reach a point when we can replace any body part we need to with a perfect biological match that we built ourselves.

READ MORE: “A New Bladder Made From My Cells Gave Me My Life Back” [BBC]

More on growing organs: The FDA Wants to Expedite Approval of Regenerative Organ Therapies

The post Lab-Grown Bladders Can Save People From a Lifetime of Dialysis appeared first on Futurism.