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Brain Tumor

Cord Blood-Derived Natural Killer Cells Complexed with Bispecific Antibody Show High Response Rates in Patients with Lymphoma

A novel cell therapy approach using cord blood-derived natural killer (NK) cells pre-complexed with AFM13, or acimtamig, a CD30/CD16A bispecific antibody, was safe and generated strong response rates for patients with refractory CD30-positive lymphomas, according to a new study.

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Cord blood-derived natural killer (NK) cells complexed with bispecific antibody AFM13 have shown high response rates in patients with refractory CD30-positive lymphomas. A recent study from The University of Texas MD Anderson Cancer Center published in Nature Medicine demonstrated an overall response rate of 92.9% and a complete response of 66.7% in heavily pretreated patients.

The trial used AFM13, a CD30/CD16A bispecific antibody designed to bind to NK cells and lymphoma cells. This unique approach pre-complexed the NK cells with AFM13 before infusion into patients, allowing for more efficient targeting and elimination of cancer cells.

“We observed rapid and strong responses to this novel approach of treating patients with AFM13-NK,” said principal investigator Yago Nieto, M.D., Ph.D. “These data lend support to this approach being considered as a possible curative treatment for some patients and a bridge to a stem cell transplant for others.”

The trial enrolled 42 adult patients with CD30-positive Hodgkin lymphoma or T-cell lymphoma, who were heavily pretreated and refractory to brentuximab vedotin and anti-PD1 immune checkpoint inhibitors. Patients received two to four cycles of chemotherapy followed by AFM13-NK cell infusion at three dose levels.

The overall response rate (ORR) was 92.9%, with a complete response (CR) of 66.7%. Among patients with Hodgkin lymphoma, the ORR and CR were 97.3% and 73%, respectively. At a median follow-up of 20 months, the two-year event-free survival (EFS) and overall survival (OS) rates for all participants were 26.2% and 76.2%, respectively.

The AFM13-NK cell treatment was well tolerated, with no cases of cytokine release syndrome, immune cell-associated neurotoxicity syndrome, or graft-versus-host disease. There was one case of Grade 2 infusion-related reaction.

“Our trial showed the favorable safety profile and encouraging activity of AFM13-NK cells in patients with heavily pretreated refractory CD30-positive Hodgkin lymphoma,” said Nieto. “This approach holds promise for the treatment of Hodgkin lymphoma and supports future research into the clinical applications of NK cells with bispecific engagers.”

Brain Tumor

“Revolutionizing Lymphoma Treatment: Enhanced CAR T Cell Therapy Shows Promise in Small Study”

A phase I study of a next-generation CAR T cell therapy showed a 52 percent complete remission rate for patients with relapsed/refractory lymphoma.

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The article describes a groundbreaking study that has shown promising results in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, including commercially available CAR T cell therapies. The new enhanced CAR T cell therapy, dubbed huCART19-IL18, was found to be highly effective in 81% of patients and resulted in complete remission in 52%. This is a significant improvement over traditional CAR T cell therapies, which have been shown to result in long-term remission in only around 50% of patients.

The study, led by researchers at the University of Pennsylvania, used a new process that shortens the manufacturing time for the CAR T cells to just three days. This means that patients with aggressive, fast-growing cancers can begin CAR T cell therapy quicker than is currently possible with standard manufacturing times of nine to 14 days.

The addition of interleukin 18 (IL18) to the CAR T cells enhanced their ability to attack cancer cells and protected them from immune suppression and T cell exhaustion. The researchers also found that the type of CAR T cell therapy patients previously received may impact the efficacy of huCART19-IL18.

This study represents a significant development in the ongoing evolution of CAR T cell therapy, as it is the first time a cytokine-enhanced CAR T has been tested in patients with blood cancer. The researchers believe that incorporating cytokine secretion into CAR T cell design will have broad implications for enhancing cellular therapies, even beyond blood cancers.

The study has already led to several other clinical trials being planned, including studies for acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Another trial for non-Hodgkin’s lymphoma using a similar IL18-armored CAR T cell product is currently enrolling patients. On the manufacturing side, the team is partnering with a Penn spinout company to improve the process for how these CAR T cells are created and expanded in the laboratory before being reinfused into the patient.

Overall, this study has shown promise in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, and further research is needed to fully understand its potential.

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Biochemistry

A Breakthrough in Brain Research: The Iontronic Pipette Revolutionizes Neurological Studies

Researchers have developed a new type of pipette that can deliver ions to individual neurons without affecting the sensitive extracellular milieu. Controlling the concentration of different ions can provide important insights into how individual brain cells are affected, and how cells work together. The pipette could also be used for treatments.

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The development of an iontronic pipette at Linköping University has opened up new avenues for neurological research. This innovative tool allows researchers to deliver ions directly to individual neurons without affecting the surrounding extracellular milieu. By controlling the concentration of various ions, scientists can gain valuable insights into how brain cells respond to different stimuli and interact with each other.

The human brain consists of approximately 85-100 billion neurons, supported by a similar number of glial cells that provide essential functions such as nutrition, oxygenation, and healing. The extracellular milieu, a fluid-filled space between the cells, plays a crucial role in maintaining cell function. Changes in ion concentration within this environment can activate or inhibit neuronal activity, making it essential to study how local changes affect individual brain cells.

Previous attempts to manipulate the extracellular environment involved pumping liquid into the area, disrupting the delicate biochemical balance and making it difficult to determine whether the substances themselves or the changed pressure were responsible for the observed effects. To overcome this challenge, researchers at the Laboratory of Organic Electronics developed an iontronic micropipette measuring only 2 micrometers in diameter.

This tiny pipette can deliver ions such as potassium and sodium directly into the extracellular milieu, allowing scientists to study how individual neurons respond to these changes. Glial cell activity is also monitored, providing a more comprehensive understanding of brain function.

Theresia Arbring Sjöström, an assistant professor at LOE, highlighted that glial cells are critical components of the brain’s chemical environment and can be precisely activated using this technology. In experiments conducted on mouse hippocampus tissue slices, it was observed that neurons responded dynamically to changes in ion concentration only after glial cell activity had saturated.

This research has significant implications for neurological disease treatment. The iontronic pipette could potentially be used to develop extremely precise treatments for conditions such as epilepsy, where brain function can be disrupted by localized imbalances in ion concentrations.

Researchers are now continuing their studies on chemical signaling in healthy and diseased brain tissue using the iontronic pipette. They also aim to adapt this technology to deliver medical drugs directly to affected areas of the brain, paving the way for more targeted treatments for neurological disorders.

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Brain Tumor

Hair-like Electrodes Revolutionize Brain Activity Monitoring

Researchers have created a hairlike device for long-term, non-invasive monitoring of the brain’s electrical activity. The lightweight and flexible electrode attaches directly to the scalp and delivers stable, high-quality electroencephalography (EEG) recordings.

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In the realm of electroencephalography (EEG) monitoring, researchers at Penn State have made a groundbreaking discovery – one that could revolutionize the way we monitor brain activity. Gone are the days of cumbersome metal electrodes; instead, a team of scientists has created hair-like devices for non-invasive, long-term monitoring.

The innovative electrode is designed to mimic human hair and can be worn without drawing attention. This lightweight and flexible device captures stable, high-quality recordings of the brain’s signals for over 24 hours of continuous wear. The traditional metal electrodes used in EEG monitoring are rigid and can shift when someone moves their head, compromising data uniformity.

The new electrode uses a 3D-printed bioadhesive ink that allows it to stick directly onto the scalp without any gloopy gels or skin preparation. This minimizes the gap between the electrode and skin, improving signal quality. The device is also stretchable, ensuring it stays put even when combing hair or wearing a baseball cap.

The researchers found that the new device performed comparably to gold electrodes, the current standard for EEG monitoring. However, the hair-like electrode maintained better contact between the electrode and skin and performed reliably for extended periods without any degradation in signal quality.

According to Tao Zhou, Wormley Family Early Career Professor of Engineering Science and Mechanics, this technology holds promise for use in consumer health and wellness products, as well as clinical healthcare applications.

The conventional EEG monitoring process can be a cumbersome affair, requiring the application of gels to maintain good surface-to-surface contact between the electrodes and skin. This process is imprecise and can result in different amounts of gel used on the electrodes, affecting brain signal quality.

Zhou explained that this new device will change the impedance – or interface – between the electrodes and scalp, ensuring more consistent and reliable monitoring of EEG signals. The researchers also hope to make the system wireless in the future, allowing people to move around freely during recording sessions.

The team’s findings were published in a study in npc biomedical innovations, with funding from various institutions, including the National Institutes of Health and Oak Ridge Associated Universities.

In conclusion, the development of hair-like electrodes for brain activity monitoring is a significant breakthrough that could revolutionize the field. With its potential for non-invasive, long-term monitoring, this technology has far-reaching implications for healthcare and consumer products alike.

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