STAT+: Allogene Therapeutics’ CAR-T treatment eliminates residual cancer cells in B-cell lymphoma patients

Allogene Therapeutics said Monday that its off-the-shelf CAR-T treatment eliminated residual cancer cells in patients with B-cell lymphoma three times better than standard care — achieving the interim goal of an ongoing Phase 3 clinical trial.

While still preliminary, the new data bolster Allogene’s efforts to develop an easily administered cell therapy that, for the first time, could delay or prevent the recurrence of cancer in patients with a high risk of lymphoma relapse at the end of first-line treatment.

In the interim analysis, 58% of patients treated with the Allogene CAR-T, called cema-cel, achieved minimal residual disease, or MRD, negativity compared to 16% of patients who were observed but not treated.

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STAT+: Spyre Therapeutics IBD drug shows promise in early trial

An inflammatory bowel disease treatment developed by Spyre Therapeutics succeeded in its first major test, setting the company up to compete with several large drugmakers developing new medicines for the chronic digestive condition. 

Spyre is currently running a Phase 2 trial testing three experimental ulcerative colitis drugs as standalone treatments and, eventually, as combination therapies. The company released the first batch of results Monday on one of the treatments, showing it was safe and met the primary goal of the study. 

The therapy, SPY001, targets the alpha 4 beta 7 inflammation pathway, one of the emerging avenues drugmakers are probing to reduce inflammation in the gut. In Spyre’s SKYLINE study, subjects taking SPY001 saw a 9.2 point decrease in a disease activity index. Approximately 40% of the trial subjects went into remission after 12 weeks of use. 

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You have no choice in reading this article—maybe

Uri Maoz loved doing his human research, back when he was getting his PhD. He was studying a very specific topic in computational neuroscience: how the brain instructs our arms to move and how our gray matter in turn perceives that motion. 

Then his professor asked him to deliver an undergrad lecture. Maoz assumed his boss was going to tell him exactly what to do, or at least throw some PowerPoint slides his way. But no. Maoz had free rein to teach anything, as long as it was relevant to the students. “I could have gone to human brain augmentation,” he says. “Cyborgs or whatever.”

Yet that admittedly fun and borderline sci-fi topic wasn’t what popped, unbidden, into his mind. His idea, he recalls with excitement: “What neuroscience has to say about the question of free will!” 

How—or whether—humans make decisions (like, say, about what to discuss in an undergrad lecture) had been on his mind since he’d read an article in his early twenties suggesting that … maybe they didn’t. This question might naturally beget others: Had he even had a choice about whether to read that article in the first place? How would he ever know if he was responsible for making decisions in his life or if he just had the illusion of control?

“After that, there was no turning back,” says Maoz, now a professor at Chapman University, in California. He finished his PhD work in human movement, but afterward he scooted further up the neural chain to find out how desires and beliefs turn into actions—from raising an arm to choosing someone to ask out to dinner on a Friday night.

Today, Maoz is a central figure in the attempt to (sort of, maybe) answer how that neural chain functions. His research has since overturned and reinter­preted canonical neuroscience studies and united the straight-scientific and philosophical sides of the free-will question. More than anything, though, he’s succeeded in uncovering new wrinkles in the debate.

Machines and magic tricks

The concept of free will seems straightforward, but it doesn’t have a universally accepted definition. One intuitive notion is that it’s the ability to make our own decisions and take our own actions on purpose—that we control our lives. But physicists might ask if the universe is deterministic, following a preordained path, and if human choices can still happen in such a universe. 

That’s a question for them, Maoz says. What neuroscientists can do is figure out what’s going on in the brain when people make decisions. “And that’s what we’re trying to do: to understand how our wishes, desires, beliefs, turn into actions,” he says.

By the time Maoz had finished his PhD, in 2008, neuroscientific research into the question had been going on for decades. One foundational study from the 1960s showed that a hand movement—something a person seemingly decides to do—was preceded by the appearance in the brain of an electrical signal called the “readiness potential.” 

Building on that result, in the 1980s a neuroscientist named Benjamin Libet did the experiment that had first piqued Maoz’s interest in the topic—one that many, until recently, interpreted as a death knell for the concept of free will.

An electrical impulse in our brains can shed only so much light on whether we truly are the architects of our own fates.

“He just had people sit there, and whenever they feel like it, they would go like this,” says Maoz, wiggling his wrist. Libet would then ask where a rotating dot was on a screen when they first had the urge to flick. He found that the readiness potential appeared not only before they moved their hand but before they reported having the urge to move—or, in Libet’s interpretation, before they knew they were going to move. 

Studies since have confirmed the observation and shown that the readiness potential appears a second or two—and maybe, fMRI implies, up to 10 seconds—before participants report making a conscious decision. “It suggests we are essentially passengers in a self-driving car,” says Maoz. “The unconscious biological machine does all the steering, but our conscious mind sits in the driver’s seat and takes the credit.” 

Maoz initially approached his own research with variations on Libet’s experiments. He worked with epilepsy patients who already had electrodes in their brains, for clinical purposes, and was able to predict which hand they would raise before they raised it. 

Still, some of the Libet-inspired studies people were doing nagged at him. “All these results were about completely arbitrary decisions. Raise your hand whenever you feel like it,” he says. “Why? No reason.” A decision like that is quite different from, say, choosing to break up with your partner. Try telling someone they weren’t in the driver’s seat for that

The field wasn’t looking at meaningful decisions, he says—the ones that actually set the course of lives. 

Maoz began pulling in philosophers to help guide his approach. They would challenge him to confront the semantic differences between things like intention, desire, and urge. Neuroscientists have tended to lump those concepts together, but philosophers tease them apart: Desire is a want that doesn’t necessarily progress toward an action; urge carries implications of immediacy and compulsion; and intention involves committing to a plan. (Maoz has come to focus specifically on intention—including, recently, the potential intentions of AI.)

In 2017, he organized his first in a series of free-will conferences, drawing many autonomy-interested philosophers. “Thank you so much for coming,” he recalls saying at the opening of the meeting. “As if you had a choice.” One day, the crew took an excursion out on a lake. As the group munched on shrimp, someone joked that they hoped the boat didn’t sink, because everybody in the field would die. 

The comment didn’t make Maoz feel existential dread. Instead, he figured that if the whole field was already there, why not lasso them all into writing a research grant? “He just thinks what should be the next step and just has a very good ability to just make it happen,” says Liad Mudrik, a neuroscientist at Tel Aviv University and a frequent collaborator.

That ability is special among scientists, says Chapman colleague Aaron Schurger, with whom Maoz co-directs the Laboratory for Understanding Consciousness, Intentions, and Decision-Making (LUCID, appropriately). “I really think that Uri is kind of at the nexus of this field right now because he’s really, really good at bringing people together around these big ideas,” he says.

Donations and interruptions

Maoz has recently been making progress on one of the big ideas that have consistently occupied his working hours: how trivial and significant decisions play out differently in the brain. In collaborations with Mudrik, he’s parsed the neural difference between picking and choosing—their terms for arbitrary decisions and those that change your life and tug on your emotions. 

Readiness potential? Their measurements didn’t clock it ahead of choices. In 2019, Maoz and a crew published a paper measuring the electrical activity in people’s brains as they pressed a key to choose one of two nonprofits to donate $1,000 to—for real, with actual dollars. Then the researchers compared that activity with what they saw when the same group pressed a key at random to donate $500 each to two nonprofits. The team saw the readiness potential in the arbitrary decision, but not for the $1,000 question. 

Libet’s result, they concluded, doesn’t apply to the important stuff, which means readiness potential might not actually be a sign that your brain is making a choice before you’re aware of it. “If Libet would have chosen to focus on deliberate decisions, then maybe the entire debate about neuroscience proving free will to be an illusion would have been spared from us,” Mudrik says. 

Maoz’s research has spurred others to reinterpret Libet’s work. It’s “enriched my thought process a great deal,” says Bianca Ivanof, a psychologist whose dissertation scrutinized Libet’s methods. They turn out to identify readiness potential at different times depending on how the rotating-dot setup is designed, complicating the ability to compare and interpret results.

Maoz has also continued to gather data on the subject. Last year, for example, he used an EEG to measure electrical signals in people’s brains as they got ready to press a keyboard space bar. At random moments, he interrupted their preparations with an audible tone and asked them about their intentions. He saw no connection between the readiness potential and whether or not they were planning to tap the key—evidence that the potential doesn’t represent the buildup of either conscious or unconscious plans. The team did see a signal, though, in a different part of the brain when people said they were preparing to move.

So … that’s free will? Sadly, Maoz would be compelled to say Well, not exactly. An electrical impulse in our brains can shed only so much light on whether we truly are the architects of our own fates. And maybe the confusing data from neurons is actually the point. “I don’t think it is a yes-or-no question,” Maoz says. Maybe our less meaningful choices aren’t mindfully made but big ones are; maybe we have the conscious power to change an intended action, but only if our brains are in a particular state. 

Neuroscientists likely can’t figure out, on their own, if free will exists. But they can, Maoz says, parse how semantically distinct decision-making forces—desires, urges, intentions, wishes, beliefs—manifest in our brains and become actions. “That is something that we are making progress on,” he says, “and I think that that’s going to help us understand what we do control.” And perhaps also help us make peace with what we do not. 

Sarah Scoles is a freelance science journalist and author based in southern Colorado.

Job titles of the future: Wildlife first responder

Grizzly bears have made such a comeback across eastern Montana that in 2017, the state hired its first-ever prairie-based grizzly manager: wildlife biologist Wesley Sarmento. 

For some seven years, Sarmento worked to keep both the bears, which are still listed as threatened under the Endangered Species Act, and the humans, who are sprawling into once-wild spaces, out of trouble. Based in the small city of Conrad, population 2,553, he acted sort of like a first responder, trying to defuse potentially dangerous situations. He even got caught in some himself—which is why, before he left the role to pursue a PhD, he turned to drones to get the job done. 

The bear necessities

Sarmento was studying mountain goats in Glacier National Park when he first started working with bears. To better understand how goats responded to the apex predator, he dressed up in a bear costume once a week for over three years. 

When he later started as grizzly manager, he often drove long distances to push bears away from farms. Bears are drawn to spilled or leaking grains, and an open silo quickly turns into a buffet. Sarmento would typically arrive armed with a shotgun, cracker shells, and bear spray, but after he narrowly escaped getting mauled one day, he knew he had to pivot.

“In that moment,” he says, “I was like, I am gonna get myself killed.”

A bird’s-eye view

Sarmento first turned to two Airedale dogs, a breed known for deterring bears on farms, but the dogs were easily sidetracked. Meanwhile, drones were slowly becoming more common tools for biologists in a range of activities, including counting birds and mapping habitats.

He first took one into the field in 2022, when a grizzly mom and two cubs were found rummaging around in a silo outside of town. The drone’s infrared sensors helped him quickly find their location, and he used the aircraft’s sound to drive them away from the property. (Researchers suspect bears instinctively dislike the whir of blades because it sounds like a swarm of bees.) “The whole thing was so clean and controlled,” he says. “And I did it all from the safety of my truck.”

Since then, the flying machine that Sarmento bought for $4,000—a fairly simple model with a thermal camera and 30 minutes of battery life—has shown its potential for detecting grizzlies in perilous terrain he’d otherwise have to approach on foot, like dense brush or hard-to-reach river bottoms.

A new technological foundation

Now studying wildlife ecology at the University of Montana, Sarmento is hoping to design a drone campus police can use to deter black bears from school grounds. In the future, he hopes, AI image recognition might be broadly integrated into his wildlife management work—maybe even helping drones identify bears and autonomously divert them from high-traffic areas.

All this helps keep bears from learning behaviors that lead to conflict with people—which typically ends badly for the bear and is occasionally fatal for humans.

“The out-of-the-box technology doesn’t exist yet, but the hope is to keep exploring applications,” he says. “Drones are the next frontier.” 

Emily Senkosky is a writer with a master’s degree in environmental science journalism from the University of Montana.

Opinion: Sports betting is creating a twofold public health crisis for some young men

Below is a lightly edited, AI-generated transcript of the “First Opinion Podcast” interview with Isaac Rose-Berman. Be sure to sign up for the weekly “First Opinion Podcast” on Apple PodcastsSpotify, or wherever you get your podcasts. Get alerts about each new episode by signing up for the “First Opinion Podcast” newsletter. And don’t forget to sign up for the First Opinion newsletter, delivered every Sunday.

Torie Bosch: Even if, like me, you don’t follow sports, it’s been impossible to miss the explosion in sports betting in recent years. With that rise is coming a new challenge for public health.

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Opinion: What STAT readers think about nutrition education in med school

First Opinion is STAT’s platform for interesting, illuminating, and provocative articles about the life sciences writ large, written by biotech insiders, health care workers, researchers, and others.

To encourage robust, good-faith discussion about issues raised in First Opinion essays, STAT publishes selected Letters to the Editor received in response to them. You can submit a Letter to the Editor here, or find the submission form at the end of any First Opinion essay.

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Epigenetics at Birth Links Microbiome to Neurodevelopment, Potentially ASD and ADHD

The results of a study headed by researchers at Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, indicate that the gut microbiome and epigenetics are intertwined, and that both contribute to neurodevelopment.

The researchers showed that epigenetic changes present at birth can impact how an infant’s gut microbiome develops during their first year. They also identified specific epigenetic changes and gut microbes that were associated with signs of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) when the children were three years old.

“Certain bacteria seem to offer protection, which is exciting because it suggests there could be ways to support a child’s development through diet or probiotics in the future,” said research lead and gastroenterologist Francis Ka Leung Chan, MD. Chan is co-senior author of the team’s published paper in Cell Press Blue, titled “Epigenome-microbiome interplay in early life associates with infants’ neurodevelopmental outcomes,” in which they stated, “We showed that epigenetic alterations at birth were associated with early-life microbiome development and that they determine the risks of neurodevelopmental consequences in children.”

The first years of life are critical for brain development and immune system maturation. Though previous studies have shown that both early epigenetic changes and gut microbiome development can impact health in later life, little is known about how these two systems interact. “Recent data suggest that epigenetic programming of gene expression profiles is sensitive to the early-life environment and can impact health outcomes in children,” the authors wrote. “One environmental cue known to trigger host epigenetic modifications is the genes of bacteria, fungi, and viruses inside the human body, collectively known as the microbiome.”

Co-senior author and public health researcher Hein Min Tun, PhD, of The Chinese University of Hong Kong, commented, “We wanted to see how the epigenome and microbiome interact in early life and if their interaction could influence a child’s risk of developing neurodevelopmental conditions like ASD and ADHD.” The authors added, “New understanding of host-microbe-epigenome interactions and mechanisms of epigenetic changes in early life can be leveraged for the prevention, early detection, and novel interventions of common childhood diseases.”

For their study the researchers characterized DNA methylation patterns from the umbilical cord blood of 571 infants. They paired this information with gut microbiome data collected from 969 infants at two, six, and 12 months of age, and from their parents during the third trimester of pregnancy. When the children reached 36 months of age, the researchers used a behavioral questionnaire to assess their neurodevelopment and investigate links between the microbiome, epigenome, and early signs of ASD and ADHD.

“This, to our knowledge, represents the first longitudinal study with multiple sample types to depict the intimate interplay between perinatal exposures, epigenetic hallmarks, and gut microbiome development and neurodevelopmental outcomes within the first three years of life,” the authors stated.

They found that an infant’s epigenome at birth was associated with birth mode, length of gestation, having older siblings, and maternal allergies, but it was not affected by their parents’ gut microbiomes. Microbiome development, on the other hand, was associated with birth mode, antibiotics, having older siblings, and breastfeeding. Infants who were born by Caesarean section (CS) showed different patterns of DNA methylation for several genes involved in immune responses and brain development. “Some of the changes in methylations of immune- and nervous-system-related genes, associated with CS delivery, are linked to neurodevelopmental outcomes,” they noted.

Their reported findings, the team suggested, “… resonate with studies linking CS to increased risks of immune-mediated and neurodevelopmental disorders, providing mechanistic plausibility through epigenomic and microbial dysbiosis.” The team also showed that an infant’s epigenome at birth impacted how their microbiome developed during their first year. Specifically, infants developed less diverse gut microbiomes at 12 months of age when they showed higher rates of DNA methylation in immune genes involved in recognizing pathogens. “We found that methylation rates in the major histocompatibility complex (MHC) region of infants at birth were linked to differences in the diversity of the infant gut microbiome at 12 months,” they commented.

The behavioral survey revealed that signs of ASD and ADHD in three-year-olds were associated with specific epigenetic patterns and the presence of certain gut microbes. “Importantly, we reported that epigenetic modifications were associated with an increased susceptibility to neurodevelopmental conditions in children, and these effects were in part mediated by microbial colonization.”

However, other microbial species seemed to mitigate these effects: infants with epigenetic patterns associated with ASD or ADHD were less likely to show signs of the disorders if they acquired Lachnospira pectinoschiza and Parabacteroides distasonis, respectively, during their first year. “We discovered a kind of conversation happening: a baby’s epigenetic setting at birth can influence their risk for neurodevelopmental disorders, but the presence of certain ‘good’ bacteria in their gut can step in and modify the risk,” Tun reported. “The foundations for brain health are laid very early, even before birth. However, we don’t want people to think this means a child’s developmental path is fixed at birth. These are complex conditions with many causes, and we’ve only uncovered a small piece of a very large puzzle.”

The researchers are continuing to follow the children who participated in the study to see how these early-life factors relate to their health as they grow. They note that laboratory experiments are needed to confirm the associations between gut microbes and neurodevelopment. In their discussion, the team wrote, “In conclusion, our findings revealed dual alterations to the neonatal epigenome and gut microbiome by perinatal factors and highlight the role of the ‘holo-epigenome’—the integrated host epigenome and microbiome—as a key mediator of neuro-immune outcomes. Interventions targeting microbial restoration or epigenetic modulation during critical developmental windows may mitigate risks of neurodevelopmental disorders.”

First author and gastroenterologist Siew Chien Ng, MD, PhD, added, “The ultimate goal is to develop safe, non-intrusive early interventions such as specific probiotics or live biotherapeutics, that could help nurture a healthy gut microbiome and potentially reduce the risk of neurodevelopmental challenges.”

The post Epigenetics at Birth Links Microbiome to Neurodevelopment, Potentially ASD and ADHD appeared first on GEN – Genetic Engineering and Biotechnology News.

GAO report shows gap between scale of illegal vapes and enforcement 

With thousands of illegal e-cigarettes for sale in the U.S., both the Trump and Biden administrations have vowed to crack down on the illicit fruit- and candy-flavored vapes that hold particular appeal to minors. But a new government report suggests law enforcement efforts by the Department of Justice lag far behind the scope of the problem. 

Most DOJ enforcement actions between fiscal year 2022 and fiscal year 2025 — 50 out of a total of 88 — were to add the names of remote e-cigarette sellers to a list of unauthorized businesses, according to the report from the Government Accountability Office. The second-most common type of enforcement actions (20 out of 88) noted in the report were injunctions to stop legal violations. 

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STAT+: Replimune skin cancer drug that became FDA flashpoint is rejected again

The Food and Drug Administration on Friday rejected — again — an experimental treatment for advanced skin cancer developed by Replimune Group. 

Replimune’s treatment, an engineered virus designed to rev up the immune system against melanoma, has been a flashpoint in a simmering debate over shifting standards at the agency.

The drug was initially rejected in July, just two months after Vinay Prasad was appointed the FDA’s head of biologics. As an academic oncologist, Prasad criticized regulators for approving drugs with limited data, and the Replimune decision was viewed as a possible sign of the stricter stance he might take at the agency.

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What’s in a name? Moderna’s “vaccine” vs. “therapy” dilemma

Is it the Department of Defense or the Department of War? The Gulf of Mexico or the Gulf of America? A vaccine—or an “individualized neoantigen treatment”?

That’s the Trump-era vocabulary paradox facing Moderna, the covid-19 shot maker whose plans for next-generation mRNA vaccines against flus and emerging pathogens have been dashed by vaccine skeptics in the federal government. Canceled contracts and unfriendly regulators have pushed the Massachusetts-based biotech firm to a breaking point. Last year, Robert F. Kennedy Jr., head of the Department of Health and Human Services, zeroed in on mRNA, unwinding support for dozens of projects—including a $776 million award to Moderna for a bird flu vaccine. By January, the company was warning it might have to stop late-stage programs to develop vaccines against infections altogether.

That raises the stakes for a second area of Moderna’s research. In a partnership with Merck, it’s been using its mRNA technology to destroy tumors through a very, very promising technique known as a cancer vacc—

“It’s not a vaccine,” a spokesperson for Merck jumped in before the V-word could leave my mouth. “It’s an individualized neoantigen therapy.”

Oh, but it is a vaccine. And here’s how it works. Moderna sequences a patient’s cancer cells to find the ugliest, most peculiar molecules on their surface. Then it packages the genetic code for those same molecules, called neoantigens, into a shot. The patient’s immune system has its orders: Kill any cells with those yucky surface markers.

Mechanistically, it’s similar to the covid-19 vaccines. What’s different, of course, is that the patient is being immunized against a cancer, not a virus.

And it looks like a possible breakthrough. This year, Moderna and Merck showed that such shots halved the chance that patients with the deadliest form of skin cancer would die from a recurrence after surgery.

In its formal communications, like regulatory filings, Moderna hasn’t called the shot a cancer vaccine since 2023. That’s when it partnered up with Merck and rebranded the tech as individualized neoantigen therapy, or INT. Moderna’s CEO said at the time that the renaming was to “better describe the goal of the program.” (BioNTech, the European vaccine maker that’s also working in cancer, has shifted its language too, moving from “neoantigen vaccine” in 2021 to “mRNA cancer immunotherapies” in its latest report.)

The logic of casting it as a therapy is that patients already have cancer—so it’s a treatment as opposed to a preventive measure. But it’s no secret what the other goal is: to distance important innovation from vaccine fearmongering, which has been inflamed by high-ranking US officials. “Vaccines are maybe a dirty word nowadays, but we still believe in the science and harnessing our immune system to not only fight infections, but hopefully to also fight … cancers,” Kyle Holen, head of Moderna’s cancer program, said last summer during BIO 2025, a big biotech event in Boston.

Not everyone is happy with the word games. Take Ryan Sullivan, a physician at Massachusetts General Hospital who has enrolled patients in Moderna’s trials. He says the change raises questions over whether trial volunteers are being properly informed. “There is some concern that there will be patients who decline to treat their cancer because it is a vaccine,” Sullivan told me. “But I also felt it was important, as many of my colleagues did, that you have to call it what it is.”

But is it worth going to the mat for a word? Lillian Siu, a medical oncologist at the Princess Margaret Cancer Centre, in Toronto, who has played a role in safety testing for the new shots, watches US politics from a distance. She believes name change is acceptable “if it allows the research to continue.”

Holen told me the doctors complaining to Moderna were basically motivated by a desire to defend vaccines—which are, of course, among the greatest public health interventions of all time. They wanted the company to stand strong. 

But that’s not what’s happening. When Moderna’s latest results were published in February, the paper’s main text didn’t use the word “vaccine” at all. It was only in the footnotes that you could see the term—in the titles of old papers and patents.

All this could be a sign that Kennedy’s strategy is working. His agencies often appear to make mRNA vaccines a focus of people’s worries, impede their reach, devalue them for companies, and sideline their defenders. 

Still, Moderna’s strategy may be working too. So far, at least, the government hasn’t had much to say about the company’s cancer vacc— I mean, its individualized neoantigen therapy.

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.