CAR T therapy works best when it activates the tumor microenvironment in a specific way, according to a study published this week in Cell. When natural killer (NK) cells are activated, survival is extended. But if regulatory T cells and immunosuppressive myeloid cells are increased, that may blunt the therapy’s effects.
“We are now working to understand the exact mechanisms underlying response and resistance so we can continue to improve treatment,” Dana Silverbush, PhD, a co-author of the study and an assistant professor of Cancer Biology at University of Pennsylvania and Penn’s Perelman School of Medicine, told Inside Precision Medicine. Other co-authors were Perelman’s Zev Binder, MD, PhD, assistant professor of neurosurgery, and Cécile Alanio, MD, PhD, adjunct professor of neurosurgery.
About a year ago, Phase I clinical trials using this team’s dual-target CAR T-cell therapy improved survival in glioblastoma (GBM) tumor treatment. But the study found that the therapy was triggering tumor reduction and extending survival in some patients, but not all. Relapse remained common.
CAR T-cell therapy is a personalized immunotherapy that uses a patient’s own immune cells to treat their cancer. While successful against blood cancers, it has not yet made significant inroads against solid tumor cancers
In this latest study, a bivalent CAR T-cell therapy was delivered via intracerebroventricular (ICV) injection. This delivers the therapy directly to the cerebrospinal fluid (CSF) surrounding the patient’s brain. As a result, researchers can sample CSF around the infusion at different times and then analyze the levels of immune activation.
“ICV results in greater numbers of CAR T cells reaching the tumor and avoids the need to cross the blood-brain barrier. There are other potential benefits, such as reduced systemic circulation of CAR T cells, which may help reduce the risk of on-target/off-tumor toxicity, that make ICV administration attractive,” Silverbush said.
GBM is a dire diagnosis. It is the most common brain cancer in adults. There are no drugs approved for recurrent disease. Overall survival for newly diagnosed GBM is around 18 months.
These researchers found that while all patients’ immune systems were activated, there were key differences between those who responded to the treatment and those who did not. Patients who responded had strong activation of NK cells, linked to tumor shrinkage and longer survival. Specifically, those favorable outcomes correlated with expansion of CD56dimCD16pos cytotoxic NK cells.
Non‑responders showed increased regulatory T cells and immunosuppressive myeloid cells, which appear to blunt the therapy.
These findings point CAR T-cell therapy towards new approaches, for example, researchers can try priming patients’ immune systems with drugs that deplete regulatory cells, or try to armor the CAR T cells with proteins that shut down regulatory T cells.
“Now that we can see on a cellular level how CAR T-cell therapy significantly changes the composition of the patient’s immune system, we can begin to investigate ways to improve the therapy so that more patients might respond to the treatment and that response will last longer,” said Silverbush.
“A lot of what we know about CAR T-cell therapy comes from treating blood cancers, which behave very differently from solid tumors like glioblastoma,” said Alanio. “We can’t do frequent brain surgery on patients receiving CAR T-cell therapy to monitor the tumor’s immune environment, but the ICV gives a unique window into a patient’s cancer that wouldn’t be available if the treatment were delivered another way.”
“When we look ahead to making our dual-target CAR T-cell therapy even more effective, these findings point us in a few promising directions,” added Binde.
A vibrating capsule that assesses how nerve signals from the stomach are registered by the brain could help identify patients with anorexia at risk of relapse, a clinical trial suggests.
The findings, in JAMA Psychiatry, offers an insight into how the eating disorder affects the nervous system as well as a way to personalize and assess the success of treatment.
The results suggest that disruptions in gastrointestinal (GI) interoception—involving the detection, transmission, and processing of signals in the digestive tract—can increase the risk of anorexia returning, even if weight has normalized.
Gastric signals could therefore act as scalable biomarkers to identify who is at increased risk of relapse and track whether treatment is improving gut-brain signaling.
“People with anorexia nervosa do not simply ignore signals from the body,” explained researcher Sahib Khalsa, PhD, at the University of California, Los Angeles.
“Rather, their nervous system may process gut sensations differently, making those signals harder to detect, trust and learn from. Over time, that may contribute to the persistence of symptoms even after weight is restored.”
Khalsa and co-workers asked 62 girls and women with anorexia nervosa whose weight had been restored to healthy levels to swallow the vibrating capsule in their crossover trial.
The capsule could be remotely controlled by the researchers to produce mechanosensory stimulation of different intensities in the stomach.
Participants were asked to press a button upon sensing a vibration, with 54 patients followed up at six months after discharge from hospital and their results compared with 57 healthy control individuals.
Computational modeling was used to estimate how strongly participants anticipated feeling sensations in their stomachs, how heavily their brains depended on body signals, and how quickly they adjusted their expectations as to the presence or absence of signals.
The researchers found that participants with anorexia had abnormal GI interoception across behavioral and computational domains compared with healthy participants, despite having intact neural and physiological responses.
Participants with anorexia were less able to detect subtle stomach sensations and were more likely than others to believe there were no sensations when the pill was vibrating. They were also less likely to update those expectations when gastric signals occurred.
Patients who were more likely to ignore the stomach signals were also at increased likelihood of relapsing to the eating disorder.
“One of the most striking findings was that these differences persisted even after weight restoration,” said Khalsa.
“Recovery from anorexia nervosa isn’t just about restoring body weight. The underlying brain–body communication problems may remain and could contribute to relapse.”
The researchers conclude that their results support the use of ingestible mechanosensory probes and computer modeling as scalable tools to monitor treatment response and guide relapse prevention in eating disorders.
Jonathan D. Grinstein, PhD, North American Editor of Inside Precision Medicine, hosts a new series called Behind the Breakthroughs that features the people shaping the future of medicine. With each episode, Jonathan gives listeners access to his guests’ motivational tales and visions for this emerging, game-changing field.
Philippe Pouletty, MD, is one of Europe’s most accomplished life sciences entrepreneurs, with a track record of creating category-leading companies in both biotechnology and medical technology. Over more than three decades, he has repeatedly identified breakthrough scientific innovations, assembled world-class teams, and scaled businesses from inception to global prominence.
His most celebrated success is Abivax, the biotechnology company he founded and led as chairman for a decade. Under his leadership, Abivax evolved into a global biotechnology powerhouse, achieving an approximately $10 billion market capitalization after positive Phase III results in 2025. In 2025, the company delivered the strongest stock market performance of any European company across all sectors.
Philippe Pouletty, MD, Co-founder and CEO of Truffle Capital and Co-founder of Abivax and Carvolix. [Truffle Capital]
Today, Philippe Pouletty is applying the same entrepreneurial playbook to Carvolix, a next-generation cardiovascular MedTech company focused on heart valve disease and stroke. Carvolix is built on the strategic combination of breakthrough implant technologies, AI-powered software, and autonomous mini-robotics. The vision follows the successful Abivax model: bring together differentiated technologies, speed up industrialization, build clinical leadership, and create a company that can transform patient outcomes while attracting significant strategic and public-market value.
A physician, scientist, inventor, and venture capitalist, Philippe has founded or co-founded numerous successful life sciences companies and holds dozens of patents, including one of Stanford University’s highest-revenue-generating life sciences inventions. With Abivax and now Carvolix, he has demonstrated a rare ability to build transformative healthcare companies that combine scientific innovation, commercial scale, and lasting impact for patients worldwide.
This interview has been edited for length and clarity.
IPM: Having spent time in both Silicon Valley and Europe, what cultural or structural differences have you discovered that have given Europe an advantage in deep tech and life sciences or that may be holding it back when compared to companies in the United States?
Pouletty: In California, financial resources are virtually limitless as long as you have a company with a great mission that addresses large medical needs and markets. Unfortunately, Europe is behind. France is an excellent place to begin, with companies to hire, good engineers, management, and so on. However, raising more than €50 or €60 million is often difficult when compared to the United States. So, things have improved over the last two decades, and there are some good grants and tax breaks available to help businesses raise capital.
However, the stock market in France and Europe is not as competitive as the Nasdaq. So, while I love the United States, many French and European companies must list on Nasdaq in order to grow, remain independent, and eventually reach the commercial stage. Then it becomes an American company, often a large pharmaceutical company or one with significant innovation. Wonderful small company. Let us buy it. So that’s great for the United States and big pharmaceutical companies. However, Europe’s prospects for the next 20 years do not look promising. The challenge for Europe is that competition will primarily come from the United States, China, and, most likely, India.
Europe faces a difficult task in catching up. But, because I’m still a crazy entrepreneur who is interested in European policies, it’s time for France and Europe to do the right thing and establish independent companies. I believe what is of interest is to do things that have an impact on patients. And if you have a positive impact on patients, you will increase shareholder value; however, you should not always focus on doing an IPO or selling the company as soon as possible. What matters is developing completely novel, radical innovation that will change or prolong the lives of patients while also benefiting the environment.
IPM: As one of Europe’s standout biotech success stories, what set Abivax apart from the many biotech companies that never scale beyond promising science in Europe before venturing out west?
Pouletty: What we like to do at Abivax and Carvolix is build businesses by merging two or three of our biotech companies when much of the R&D is completed in order to reach critical mass and have several product candidates available. So if one fails, the company is not doomed. To be able to attract extremely experienced management. There are too many very small businesses in Europe. For example, the president, Emmanuel Macron, likes to refer to France as the “startup nation.” The goal should not be to become the startup nation. The goal should be to develop world leaders similar to those in the United States, regardless of sector.
Abivax emerged in 2013. Three of our biotech companies were able to complete a Euronext IPO, which remains the largest biotech IPO on Euronext. We had raised €58 million at the time. Surprisingly, the most advanced product candidate, a drug candidate, failed following the IPO in phase two. So it was unpleasant but not disastrous because the second product candidate, which was only in phase one at the time, is now assembled, has a $7 to $10 billion valuation, and has had excellent results in phase three in treating ulcerative colitis patients.
So, it appears to be a straightforward business plan. It’s not correct. You must stay focused on your mission. Disappointment can occur during pre-clinical R&D and clinical development. Of course, this happens to the majority of biotech companies. And this is why, for example, when sailing across the Atlantic or Pacific, you must keep in mind that reaching the other side requires a strong team; sometimes we change the team and the CEO.
But we are very proud to say that the above acts would not exist without Truffle Capital, and I was chairman of the board for ten years and was very pleased. it looks like the drug should be approved. In the last few days the stock dropped because the long-term maintenance clinical results showed great efficacy and there were very few cancers, which is typical in this kind of patient population with a dysfunctional immune system.
So to me, it’s a little hiccup, but I’m very confident it will change and improve the lives of the patients with ulcerative colitis. Now, maybe the little drop in valuation will boost the M&A appetite of some big pharma companies. And I can send that because, well, not any more shareholders are involved in the epilogue. It’s my personal opinion, of course, about the future. I could be wrong.
IPM: How do emerging European companies like Carvolix or Abivax compete with American or Chinese companies? Do you try to establish a market in Europe first, then expand internationally, or do you try to do everything at once? What’s your strategy there?
Pouletty: When Carvolix first launched in the United States, the largest market was heart valve software. So, while launching in the United States with a very concentrated focus team, step by step with specialized centers and then with the market, research based on this successful launch will expand. We may later hire a partner for the United States, or agents or a single partner.
We want our products to be agnostic, regardless of whether the valve is Abivax, Medtronic, or Abbott, so that hospital clinicians can choose which valve system to use for their patients with our software and robot. We will continue to conduct direct sales in Europe, as we have in the past. If you have a highly innovative product, you will need a small, highly technical sales force that can visit clinics, hospitals, and clinicians to be successful in Asia.
IPM: How do you get clinicians and hospitals to buy into something like this, which isn’t really an upgrade of their system, but rather the introduction of a whole new line?
Pouletty: At first, we assumed that top-tier cardiologists who treat hundreds or thousands of patients would not require our services. And it will primarily benefit younger, less-trained cardiologists. However, we conducted studies in France with data from the world’s leading cardiologist for aortic valve replacement, as well as in Australia with highly trained cardiologists. They said, “That’s great because I’m less stressed during the implantation.” I may not need a second cardiologist in the room, as is frequently required, and I may see more patients during the day.
It’s somewhat similar to cars. You could argue that autonomous cars will not meet the needs of taxi drivers. But yes, taxi drivers will say, “Great.” I can drive more miles, transport more passengers, and feel more relaxed at the end of the day. I have no doubt that it will become the norm in medium and small hospitals over the next few years. Place special patients in the care of an expert cardiologist. Now for given special patients in the hands of an expert cardiologist, we don’t pretend it will do better. But many more patients who have not the chance, whether it’s hardware replacement or brain stroke treatment to healthcare… will if we are successful.
It is critical to ensure that introducing AI and robotics does not prolong the procedure. It takes roughly the same amount of time or appears to be shorter. However, it is always under clinical supervision. We can take over and stop the procedure, just like on a plane, and carry it out manually. However, after some initial training with a few patients, the clinician will most likely allow the procedure to be completed autonomously while closely monitoring the screen to ensure that everything is running smoothly.
IPM: How do European healthcare systems differ in their ability to adopt new biotech and medtech innovations?
Pouletty: No system is perfect. I do a very simple comparison in France and Europe. even patients who do not work will be treated in the hospital at no cost. In the U.S., you’d better have a plan. You’re working in the company to be covered. There is no perfect system. Certainly, pricing of drugs and medical devices in the U.S. is higher, which means that there is an incentive for investors and companies to do high-cost R&D to recoup their investment through high pricing. In France and Europe, there is a tendency to have to push for low pricing and low reimbursement, which is why for oncology drugs more are available and reimbursed in the U.S. today than for non-college products.
But there is not enough emphasis on the long-term impact of innovation. And pioneers often looked at the shorter impact and said, oh, that’s two weeks, let’s say. I’ll give you one example. In oncology, pancreatic cancer is tough because the diagnosis is very often very late when you have big tumors.
It’s very clear that if it were up to me, we would do imaging every two years. We would catch very small, tiny tumors very early on because an anatomical change in our cells within two years could indicate that you need to go and see if you should remove this little tiny one. But that’s not common in practice because it would be expensive to do an MRI every two years on everyone after 50 years old.
So beyond drugs and medical devices and the practice of medicine, how do you do? Preventative medicine needs to be greatly improved, and governments are not very good at looking at these approaches to improve healthcare. So, I went into politics. I would turn on that. I decided 25 years ago I would not run for any elected office and focus more on starting companies.
IntroductionMoral injury, the psychological harm resulting from events that violate one’s deeply held moral beliefs, has been extensively studied in military and healthcare populations but remains largely unexamined among animal care workers.MethodsThis cross-sectional survey of 291 animal care workers across six sectors (rescue, shelter, animal control, veterinary medicine, volunteer/foster, and other) provides the first empirical prevalence estimate of moral injury in this cross-sector population using a validated syndrome measure.ResultsFindings from the Moral Injury Outcome Scale (MIOS) indicate that 83.5% of participants endorsed at least one morally injurious experience pathway; most common was witnessing (63.9%), followed by being affected by others’ transgressions (38.5%) and direct participation (29.2%). Applying published caseness thresholds, 18.9% of the potentially morally injurious event (pMIE) endorsers met criteria for moral injury as a clinical syndrome and an additional 21.4% for moral distress (subclinical), with blended shame and trust violation presentations characterizing the majority (53.1%) of clinical cases. Patient Health Questionnaire-9 scores exceeded the clinical threshold for moderate depression (M = 10.96, SD = 6.27). One-way analysis of variance revealed significant sector differences in functional impairment, trust violations, and depression, with shelter workers reporting the highest levels across nearly all measures. The MIOS Shame subscale was more strongly associated with both depression (r = .646) and functional impairment (r = .343) than the Trust Violations subscale, which showed no significant relationship with functional impairment (r = .045, p = .456). Endorsement of the direct participation pathway was the only exposure pathway significantly associated with caseness classification, with 31.8% of direct participation endorsers meeting criteria for moral injury compared to 12.0% of non-endorsers (p < .001). A departure from standard MIOS administration presenting impact items to all participants revealed that a small number of pMIE non-endorsers met caseness thresholds despite actively denying exposure, raising questions about the comprehensiveness of current pathway categories.DiscussionThese findings identify moral injury as a prevalent and clinically significant occupational experience among animal care workers, with distinct shame-based and trust violation-based mechanisms in predicting functional decline and clinical severity, respectively. Implications for targeted intervention and organizational reform are discussed.
CAR T cell therapy can induce deep responses but also severe toxicities in patients with smoldering myeloma, an asymptomatic cancer precursor; given the potential risks and benefits, its success depends on careful patient selection.
With its biomedicine at an inflection point, India can seize the opportunity to scale up research and development at home and offer a distinct model of biomedical innovation for the global south.
In my view, we have never had as robust a body of evidence from observational data on an intervention for dementia as we do for live-attenuated shingles vaccination. Both a recent US National Institutes of Health expert workshop and an international expert consensus on Alzheimer’s disease drug repurposing identified large-scale randomized trials of shingles vaccination for dementia prevention as the crucial next step for the field.
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My colleague Eric Boodman’s stories usually make me cry as well, but his recent article about babies being born with congenital syphilis, which is usually totally preventable with penicillin from Pfizer, made me want to tear my hair out.
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Good morning. The season finale of the “First Opinion Podcast” airs today. Sarah Mupo, STAT’s director of editorial operations and lead gal in charge of the style guide, joined Torie Bosch to discuss the decision to keep “health care” two words. Take a listen.
The Danaher Bioprocessing Summit, “The Next Era of Bioprocessing: From Promise to Patient Impact,” took place in London earlier this month. The event brought together officials from Danaher companies (Cytiva, Pall, Beckman Coulter Life Sciences, IDBS, and Leica Microsystems), along with biopharma manufacturers and researchers to discuss how the industry can accelerate the transition from scientific breakthroughs to commercial therapies.
Key themes included:
AI-driven bioprocess development and manufacturing
Intensified and continuous bioprocessing
Digitalization and connected data ecosystems
Improving productivity and reducing cost of goods
Cell and gene therapy manufacturing challenges
Scaling production of high-demand biologics, including GLP-1 therapies
Advanced analytics and process control
Sustainability in biomanufacturing
The conference emphasized that future competitive advantage in biomanufacturing will come less from building additional capacity and more from increasing productivity, speed, and process intelligence across the development-to-manufacturing workflow.
Based on the formal presentations, roundtable discussion groups, and conversations among speakers, panelists, and attendees, six key takeaway ideas emerged.
The old manufacturing playbook no longer fits
Biomanufacturing was built for large batches of standardized therapies. The next generation of medicines—cell and gene therapies, targeted and complex biologics, N-of-1 treatments—doesn’t fit that mold. As molecular diversity increases, the field is shifting toward smaller, parallel and distributed systems that can flex to meet the complexity of individualized medicine. This means faster decision-making, new investment models, and process designs that are data-driven and purpose-built from the start rather than adapted from previous playbooks.
Manufacturing can no longer be treated as a downstream problem. It has to be part of the scientific conversation from day one.
Automation and AI are making personalized scale possible
For years, the promise of personalized medicine ran into a hard wall: you can’t manufacture one patient’s therapy the same way you manufacture a million doses of a traditional drug. Integrating automation, AI and high-throughput experimentation is changing that equation.
These tools are enabling a shift from large-batch production to small-batch and even patient-specific manufacturing while improving efficiency, regulatory consistency, and access to advanced therapies. AI and digital tools are also compressing process development timelines, making it possible to design more tailored, adaptive manufacturing approaches without sacrificing rigor.
Prediction is becoming a competitive advantage
The organizations gaining ground are not merely reacting to problems faster but actually anticipating them. Digital twins powered by integrated data are helping teams model outcomes before committing resources, accelerating timelines and reducing risk. And real-time, molecular and submolecular-level data—shared across interoperable systems—are enabling more precise, proactive decision-making at every stage of development and manufacturing. Investing in this area with critical infrastructure is essential.
Breakthroughs require collaboration across the whole ecosystem
It turned out that the most consistent theme across both days of the Summit was this: no single organization can accomplish what’s needed alone. Partnerships across academia, industry, and regulators are accelerating how all kinds of therapies, especially gene therapies, move from discovery to approved treatment. Earlier alignment between developers, manufacturers, and regulators is reducing friction and compressing timelines.
A central theme surfaced throughout the conference: the science is not the problem. The bioindustry already possesses powerful technologies and therapeutic capabilities. Future success depends on rapidly implementing them through manufacturing, regulatory alignment, supplier collaboration, and partnerships. Organizations that execute most effectively will shape the next decade of medicine. [Danaher]
What makes these partnerships work is not goodwill alone but transparency, shared incentives, and data-driven collaboration that keeps everyone oriented around the same outcomes. The organizations making the most progress are those treating collaboration as a core capability.
Regulatory models are evolving with the science, and sustainability is now a procurement requirement, not a values statement
Most of the frameworks that currently govern drug development were built for an earlier era of medicine. As therapies grow more complex and more personalized, those frameworks must change. Early engagement and risk-based approaches are helping bring complex therapies to patients faster without compromising scientific rigor. For rare diseases, which collectively affect an estimated 300 million people worldwide, tailored regulatory pathways are becoming essential.
Summit speakers agreed that regulators are not the obstacle they’re sometimes assumed to be. They want to move faster too, and building the right collaborative infrastructure makes that possible.
Environmental and social criteria are moving from corporate commitments into day-to-day supplier decisions. Organizations are integrating sustainability standards into procurement frameworks, requiring verified supplier commitments and shared performance targets as part of doing business.
Far from being separate from operational strategy, this is part of building supply chains resilient enough to support long-term innovation at scale. Progress toward net-zero goals, Summit participants agreed, accelerates when sustainability is wired into commercial relationships rather than managed alongside them.
Across two days and numerous conversations, one key point kept surfacing: the science is not the problem. The biopharma industry has the tools, the knowledge, and the therapeutic advances to transform how medicine is made and delivered. What it lacks is the collective will to operationalize them at speed. The next phase of progress will be won in manufacturing facilities, regulatory negotiations, supplier contracts, and partnerships that connect all of them.
The final conclusion: organizations that close the gap first will define what the next decade of medicine looks like.
To watch recorded keynote presentations, panel discussions, and fireside chats from the Danaher Summit on Bioprocessing, click here.
![A central theme surfaced throughout the conference: the science is not the problem. The bioindustry already possesses powerful technologies and therapeutic capabilities. Future success depends on rapidly implementing them through manufacturing, regulatory alignment, supplier collaboration, and partnerships. Organizations that execute most effectively will shape the next decade of medicine. [Danaher]](https://www.genengnews.com/wp-content/uploads/2026/06/capacity_scale_panel_dhr_summit2026.jpg)