Tag: news coverage

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Secondary Cancers Following CAR T Cell Therapy Are Rare, Penn Medicine Analysis Shows

by Meagan Raeke

3d illustration of a damaged and disintegrating cancer cell. (Image: iStock/vitanovski)

The development of any type of second cancer following CAR T cell therapy is a rare occurrence, as found in an analysis of more than 400 patients treated at Penn Medicine, researchers from the Perelman School of Medicine at the University of Pennsylvania reported today in Nature Medicine. The team also described a single case of an incidental T cell lymphoma that did not express the CAR gene and was found in the lymph node of a patient who developed a secondary lung tumor following CAR T cell therapy.

CAR T cell therapy, a personalized form of immunotherapy in which each patient’s T cells are modified to target and kill their cancer cells, was pioneered at Penn. More than 30,000 patients with blood cancers in the United States—many of whom had few, if any, remaining treatment options available—have been treated with CAR T cell therapy since the first such therapy was approved in 2017. Some of the earliest patients treated in clinical trials have gone on to experience long-lasting remissions of a decade or more.

Secondary cancers, including T cell lymphomas, are a known, rare risk of several types of cancer treatment, including chemotherapy, radiation, and stem cell transplant. CAR T cell therapy is currently only approved to treat blood cancers that have relapsed or stopped responding to treatment, so patients who receive CAR T cell therapies have already received multiple other types of treatment and are facing dire prognoses.

In November 2023, the FDA announced an investigation into several reported cases of secondary T cell malignancies, including CAR-positive lymphoma, in patients who previously received CAR T cell therapy products. In January 2024, the FDA began requiring drugmakers to add a safety label warning to CAR T cell products. While the FDA review is still ongoing, it remains unclear whether the secondary T cell malignancies were caused by CAR T cell therapy.

As a leader in CAR T cell therapy, Penn has longstanding, clearly established protocols to monitor each patient both during and after treatment – including follow-up for 15 years after infusion – and participates in national reporting requirements and databases that track outcomes data from all cell therapy and bone marrow transplants.

Marco Ruella, M.D.

“When this case was identified, we did a detailed analysis and concluded the T cell lymphoma was not related to the CAR T cell therapy. As the news of other cases came to light, we knew we should go deeper, to comb through our own data to better understand and help define the risk of any type of secondary cancer in patients who have received CAR T cell products,” said senior author Marco Ruella, MD, an assistant professor of Hematology-Oncology and Scientific Director of the Lymphoma Program. “What we found was very encouraging and reinforces the overall safety profile for this type of personalized cell therapy.”

Read the full story in Penn Medicine News.

Marco Ruella is Assistant Professor of Medicine in the Perelman School of Medicine. He is a member of the Penn Bioengineering Graduate Group.

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Protein Partners Identified as Potential Key for Fetal Bone Development

Image: iStock/Christoph Burgstedt

A pair of proteins, YAP and TAZ, has been identified as conductors of bone development in the womb and could provide insight into genetic diseases such as osteogenesis imperfecta, known commonly as “brittle bone disease.” This research, published in Developmental Cell and led by members of the McKay Orthopaedic Research Laboratory of the Perelman School of Medicine, adds understanding to the field of mechanobiology, which studies how mechanical forces influence biology.

“Despite more than a century of study on the mechanobiology of bone development, the cellular and molecular basis largely has remained a mystery,” says the study’s senior author, Joel Boerckel, an associate professor of orthopaedic surgery. “Here, we identify a new population of cells that are key to turning the body’s early cartilage template into bone, guided by the force-activated gene regulating proteins, YAP and TAZ.”

Read the full story in Penn Medicine News.

Joel D. Boerckel is Associate Professor in Orthopaedic Surgery and in Bioengineering.

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Sonura Named Among 2023 PHL Inno Under 25 Honorees

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce

A team of recent Penn Bioengineering graduates have been included in list of prominent young Philadelphia innovators as chosen by The Philadelphia Business Journal and PHL Inno.

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce founded Sonura as their Senior Design Project in Bioengineering. The team, who all graduated in 2023, picked up a competitive President’s Innovation Prize for their beanie that promotes the cognitive and socioemotional development of newborns in the NICU by protecting them from the auditory hazards of their environments while fostering parental connection. Now, they have been included in the list of fourteen Inno Under 25 honorees for 2023.

“To determine this year’s list, the Philadelphia Business Journal and PHL Inno sought nominations from the public and considered candidates put forth by our editorial team. To be considered, nominees must be 25 years of age or younger and work for a company based in Greater Philadelphia and/or reside in the region.

Honorees span a wide range of industries, including consumer goods, biotechnology and environmental solutions. Many are products of the region’s colleges and universities, though some studied farther afield before setting up shop locally.”

Read “Announcing the 2023 PHL Inno Under 25 honorees” and “Inno Under 25” in PHL Inno. Penn affiliates can subscribe through Penn’s library services.

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Carl June on the Boundless Potential of CAR T Cell Therapy

by Meagan Raeke

Carl June, at the flash mob celebration of the FDA approval of the CAR T cell therapy he developed, in August 2017. (Image: Courtesy of Penn Medicine Magazine)

For most of modern medicine, cancer drugs have been developed the same way: by designing molecules to treat diseased cells. With the advent of immunotherapy, that changed. For the first time, scientists engineered patients’ own immune systems to recognize and attack diseased cells.

One of the best examples of this pioneering type of medicine is CAR T cell therapy. Invented in the Perelman School of Medicine by Carl June, the Richard W. Vague Professor in Immunotherapy, CAR T cell therapy works by collecting T cells from a patient, modifying those cells in the lab so that they are designed to destroy cancerous cells, and reinfusing them into the patient. June’s research led to the first FDA approval for this type of therapy, in 2017. Six different CAR T cell therapies are now approved to treat various types of blood cancers. Carl June, at the flash mob celebration of the FDA approval of the CAR T cell therapy he developed, in August 2017. (Image: Courtesy of Penn Medicine Magazine)

CAR T cell therapy holds the potential to help millions more patients—if it can be successfully translated to other conditions. June and colleagues, including Daniel Baker, a fourth-year doctoral student in the Cell and Molecular Biology department, discuss this potential in a perspective published in Nature.

In the piece, June and Baker highlight other diseases that CAR T cell therapy could be effective.

“CAR T cell therapy has been remarkably successful for blood cancers like leukemias and lymphomas. There’s a lot of work happening here at Penn and elsewhere to push it to other blood cancers and to earlier stage disease, so patients don’t have to go through chemo first,” June says. “Another big priority is patients with solid tumors because they make up the vast majority of cancer patients. Beyond cancer, we’re seeing early signs that CAR T cell therapy could work in autoimmune diseases, like lupus.”

As for which diseases to pursue as for possible future treatment, June says, “essentially it boils down to two questions: Can we identify a population of cells that are bad? And can we target them specifically? Whether that’s asthma or chronic diseases or lupus, if you can find a bad population of cells and get rid of them, then CAR T cells could be therapeutic in that context.”

“What’s exciting is it’s not just theoretical at this point. There have been clinical reports in other autoimmune diseases, including myasthenia gravis and inflammatory myopathy,” Baker says. “But we are seeing early evidence that CAR T cell therapy will be successful beyond cancer. And it’s really opening the minds of people in the field to think about how else we could use CAR T. For example, there’s some pioneering work at Penn from the Epstein lab for heart failure. The idea is that you could use CAR T cells to get rid of fibrotic tissue after a cardiac injury, and potentially restore the damage following a heart attack.”

Baker adds, “there’s no question that over the last decade, CAR T cell therapy has revolutionized cancer. I’m hoping to play a role in bringing these next generation therapies to patients and make a real impact over the next decade. I think there’s potential for cell therapy to be a new pillar of medicine at large, and not just a new pillar of oncology.”

Read the full story at Penn Medicine Today.

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Chasing the Mysteries of Microbiome Communication in Our Bodies

by Kelsey Geesler

Perelman School of Medicine’s Maayan Levy, and Christoph Thaiss. (Image: Courtesy of Penn Medicine News)

When we hear about gut bacteria, we may think about probiotics and supplements marketed to help with digestion, about how taking antibiotics might affect our intestinal tract, or perhaps about trendy diets that aim to improve gut health.

But two researchers at Penn Medicine think that understanding the microbiome, the entirety of microbial organisms associated with the human body, might be the key to deciphering the fundamental mechanisms that make our bodies work. They think these microbes may work like a call center switchboard, making connections to help different organs, biological systems, and the brain communicate. Maayan Levy, and Christoph Thaiss, both assistant professors of microbiology at the Perelman School of Medicine, argue that the microbiome is instrumental to revealing how signals from the gastrointestinal tract are received by the rest of the body—which may hold the key to understanding inter-organ communication in general. Perelman School of Medicine’s Maayan Levy, and Christoph Thaiss. (Image: Courtesy of Penn Medicine News)

While the gut sends signals to all parts of the body to initiate various biological processes, the mechanisms underlying this communication—and communication between different organs involved in these processes—is relatively unknown.

“The more we learn about the role the microbiome plays in a wide range of diseases— from cancer to neurodegenerative diseases to inflammatory diseases—the more important it becomes to understand what exactly its role is,” says Thaiss. “And hopefully once we understand how it works, we can use the microbiome to treat these diseases.”

Levy and Thaiss joined the faculty at Penn Medicine after completing their graduate studies in 2018. Here, they continue to investigate the role of the microbiome in various biological processes.

In his lab, Thaiss focuses on the impact of the microbiome on the brain. He recently identified species of gut-dwelling bacteria that activate nerves in the gut to promote the desire to exercise. Most recently, Thaiss published a study that identified the cells that communicate psychological stress signals from the brain to the gastrointestinal tract, and cause symptoms of inflammatory bowel disease.

Meanwhile, in her lab, Levy examines how the microbiome influences the development of diseases, like cancer, and other conditions throughout the body.

A recent publication authored by Levy suggested that the ketogenic diet (high fat, low carbohydrate) causes the production of a metabolite called beta-hydroxybutyrate (BHB), that suppresses colorectal cancer in small animal models.

Now, Levy is collaborating with Bryson Katona, an assistant professor of Medicine in the division of gastroenterology who specializes in gastrointestinal cancers, to investigate whether BHB has the same effect in patients with Lynch syndrome, which causes individuals to have a genetic predisposition to many different kinds of cancer, including colon cancer. These efforts are part of a growing emphasis at Penn on finding methods to intercept cancer in its earliest stages.

“It’s remarkable that we were able to quickly take the findings from our animal models and rapidly design a clinical trial,” Levy says. “One of the most exciting aspects of our work is not only making discoveries about how our bodies work on a biological level, but then being able to work with the world’s leading clinical experts to translate these discoveries into therapies for patients.”

Further, studies led by Levy and Thaiss often utilize human samples and data from the Penn Medicine BioBank, to validate animal model findings in the tissue of human patients suffering from the diseases which they are investigating.

While Levy and Thaiss pursue different research interests with their labs, they also collaborate often, building on their previous research into what the microbiome does, and its role in the biological processes that keep us healthy. Their long-term goal is to learn about the mechanisms by which the gastrointestinal tract influences disease processes in other organs to treat various diseases of the body using the gastrointestinal tract as a noninvasive entry point to the body.

“Some of the most common and devastating diseases in humans—like cancer or neurodegeneration—are difficult to treat because they are no existing therapies that can reach the brain,” says Thaiss. “If we can understand how the gastrointestinal tract interacts with other organs in the body, including the brain, we might be able to develop treatments that ‘send messages’ to these organs through the body’s natural communication pathways.”

“Obviously there is a lot more basic biology to be uncovered before we get there,” adds Levy. “Most importantly, we want to map all the different routes by which the gastrointestinal tract interacts with the body, and how that communication happens.”

Read the full story in Penn Medicine News.

Christopher Thaiss is Assistant Professor in Microbiology in the Perelman School of Medicine. He is a member of the Penn Bioengineering Graduate Group.

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Cesar de la Fuente On the “Next Frontier” of Antibiotics

César de la Fuente
César de la Fuente

In a recent CNN feature, César de la Fuente, Presidential Assistant Professor in Bioengineering, Psychiatry, Microbiology, and in Chemical and Biomolecular Engineering commented on a study about a new type of antibiotic that was discovered with artificial intelligence:

“I think AI, as we’ve seen, can be applied successfully in many domains, and I think drug discovery is sort of the next frontier.”

The de la Fuente lab uses machine learning and biology to help prevent, detect, and treat infectious diseases, and is pioneering the research and discovery of new antibiotics.

Read “A new antibiotic, discovered with artificial intelligence, may defeat a dangerous superbug” in CNN Health.

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Penn Bioengineering Graduate Student on T Cell Therapy Improvements

Image: Courtesy of Penn Medicine News

 Neil Sheppard,  Adjunct Associate Professor of Pathology and Laboratory Medicine in the Perelman School of Medicine, and David Mai, a Bioengineering graduate student in the School of Engineering and Applied Science, explained the findings of their recent study, which offered a potential strategy to improve T cell therapy in solid tumors, to the European biotech news website Labiotech.

Mai is a graduate student in the lab of Carl H. June, the Richard W. Vague Professor in Immunotherapy in Penn Medicine, Director of the Center for Cellular Immunotherapies (CCI) at the Abramson Cancer Center, and member of the Penn Bioengineering Graduate Group.

Read “Immunotherapy in the fight against solid tumors” in Labiotech.

Read more about this collaborative study here.

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Penn Medicine and Independence Blue Cross Eliminate Preapprovals for Imaging Tests

Brian Litt, MD

Brian Litt, Professor in Bioengineering in Penn Engineering and in Neurology in the Perelman School of Medicine, spoke to Neurology Today about the advances in technology for detecting and forecasting seizures.

The Litt Lab for Translational Neuroengineering translates neuroengineering research directly into patient care, focusing on epilepsy and a variety of research initiatives and clinical applications.

“Dr. Litt’s group is working with one of a number of startups developing ‘dry’ electrode headsets for home EEG monitoring. ‘They are still experimental, but they’re getting better, and I’m really optimistic about the possibilities there.'”

Read “How Detecting, Identifying and Forecasting Seizures Has Evolved” in Neurology Today.

Read more stories featuring Litt in the BE Blog.

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Penn Bioengineering Senior Design Expo Featured in Technical.ly Philly

Members of Team Sonura: Tifara Boyce, Gabriela Cano, Gabriella Daltoso, Sophie Ishiwari, & Caroline Magro (credit: Penn BE Labs)

Technical.ly Philly journalist Sarah Huffman recently paid another visit to Penn Bioengineering’s George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, this time for the 2023 Senior Design Expo. Following the annual Senior Design presentations held in the Singh Center for Nanotechnology, in which graduating fourth-year undergraduates in Bioengineering presented their final capstone projects, the Expo offered an opportunity for the teams to do live demonstrations (or demos) for the department’s internal competition judges and the wider BE community.

“In the course of the day, students presented the challenge they were aiming to solve and the technical details of their solution. After, demonstrations sought to find if the devices really worked.

‘[It’s] looking at the device as a whole, because quite frankly, you can say whatever you want at a presentation, does it really work,’ said [BE Labs Director Sevile] Mannickarottu. ‘You can make it look pretty, “but does it work?” is the big question.'”

Read “At Penn’s Senior Design Expo, students aimed to solve healthcare issues with tech devices” in Technical.ly Philly.

To learn more about the 2023 Senior Design projects, including pitch videos, abstracts, full presentations and awards, visit the Penn BE Labs Website.

Read about Technical.ly’s first visit to the Penn BE Labs here.

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Senior Design Team “StablEyes” Uses 3D Printing to Simplify Retinal Imaging

A team of Penn Bioengineering Senior Design students was featured as the 3D print of the week by the Penn Biomedical Library’s Biomeditations blog.

The StablEyes team. From left to right, Jake Becker (BE ’23), Ruoming Fan (BE ’23), Ella Atsavapranee (BE ’23), and Savan Patel (M&T ’23).

Fourth-year undergraduate students Ella Atsavapranee, Jake Becker, Ruoming Fan, and Savan Patel created StablEyes, “a stabilization mount that provides fine, motorized control of the handheld OCT to improve ease of use for physicians and machine learning-based software to aid in diagnosis from retinal images.” The team made use of 3D printing services, laboratory space, and expertise across Penn’s campus to create their innovative design, including the Bollinger Digital Fabrication Lab in the Holman Biotech Commons, the Fisher Fine Arts Library, the Children’s Hospital of Philadelphia (CHOP), and the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace (aka the Penn BE Labs).

Read “Featured 3D Print: Simplifying Retinal Imaging with StablEyes” by Lexi Voss in Biomeditations.