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CNS infiltration by zamtocabtagene autoleucel tandem CD20/CD19 CAR T cells leading to complete remission in a patient with primary CNS lymphoma

CAR T cells in primary CNS lymphoma.

Treatment options for primary central nervous system (CNS) lymphoma remain limited, particularly in relapsed or refractory disease. This case report explores the activity and CNS trafficking of tandem CD20/CD19 CAR T cells (zamtocabtagene autoleucel), addressing key questions about cellular therapy in CNS lymphoma and the potential role of dual-target CAR T strategies.

CD19-directed chimeric antigen receptor (CAR) T-cell (CAR T) therapy is a well-established treatment for B-cell malignancies, but accessibility, toxicities, lack of persistence, modest anti-tumor activity, restricted trafficking and tumor antigen escape are among its limitations.1 Concern for excessive neurotoxicity led to exclusion of patients with central nervous system (CNS) involvement from clinical trials, and primary CNS lymphoma (PCNSL) is an exclusion on the approved products’ labeling. PCNSL is a highly aggressive lymphoma, with a favorable response to initial chemotherapy/radiation, but compared with lymphomas outside the CNS, relapses are common, and survival is inferior. Moreover, there is a lack of approved standard care beyond first-line therapy and the prognosis for these PCNSL patients remains poor.2

In approximately one third of all B-cell lymphoma patients, resistance to CAR T and relapses are accompanied by CD19 downregulation. Preclinical evidence suggests that dual antigen-targeting may overcome this problem.3 To address antigen escape, the investigational anti-CD20/ anti-CD19 CAR T product MB-CART2019.1 (zamtocabtagene autoleucel [zamto-cel]) was designed. Zamto-cel is a dual-targeting tandem-CAR construct with scFv regions of anti-CD19 and anti-CD20 linked in sequence by a flexible interchain linker, followed by CD8, 4-1BB and CD3 ζ domains.4 Our group and others have evaluated zamto-cel in a pivotal phase II clinical trial (DALY II USA/ MB-CART2019.1; clinicaltrials gov. Identifier: NCT04792489) for the treatment of DLBCL patients who received at least two lines of treatment.5 In addition to addressing antigen escape/relapse zamto-cel is non-cryopreserved with a vein-to-vein time of 14 days, improving cell yield and potency.

Extreme stability in ultrafast nanomagnetism aids the development of faster data storage

For the first time, researchers have mapped how the boundaries of magnetic nanostructures behave on extremely short timescales. The work of physicist Johan Mentink of Radboud University shows that these boundaries are much more stable than previously thought. This insight will aid the development of future ultra-fast and compact data storage.

Every magnet consists of tiny magnets, known as spins. When a material is magnetic, these spins all point in the same direction. Using ultra-short laser pulses, the spins in magnetic materials can change direction in a very short time. This so-called ultrafast nanomagnetism is important for, for example, hard drives, on which information is stored using magnetic bits. To make this storage faster and smaller, it is essential to understand exactly what happens at the nanoscale.

Using a new imaging technique capable of tracking processes down to the nanometer and femtosecond scale, Mentink and colleagues have researched the behavior of domain boundaries—thin walls of about 1 nanometer that separate magnetic domains. Multiple spins pointing in the same direction form a domain.

Alien comet carries record-heavy water, and its birthplace looks nothing like our cosmic neighborhood

Less than a year ago, astronomers discovered a comet soaring through our sky that was not from our solar system. Although we still don’t know where this interstellar object called 3I/ATLAS came from, research led by the University of Michigan has revealed new insights about its birthplace. Wherever that was, it was much colder than the environment that created our solar system.

The new finding is based on the observation that 3I/ATLAS is remarkably rich in a specific type of water that contains deuterium. The team’s study is published in the journal Nature Astronomy.

“Our new observations show that the conditions that led to the formation of our solar system are much different from how planetary systems evolved in different parts of our galaxy,” said Luis Salazar Manzano, lead author of the new study and a doctoral student in the U-M Department of Astronomy.

CERN’s Medipix3 technology on track to help more patients

Originally derived from a technology developed to explore the fundamental nature of the Universe, Medipix3 technology now powers a medical scanner that is on track to benefit an increased number of patients. MARS Bioimaging Ltd has received 510(k) clearance from the US Food and Drug Administration (FDA) for its portable photon-counting CT scanner for upper-limb imaging, allowing the system to enter the US health sector and enable broader clinical adoption.

Medipix technology is based on hybrid pixel detectors, which were originally designed at CERN for particle detection in high-energy physics experiments. This technology was adapted to create the Medipix family of pixel detector readout chips, enabling a new approach to medical imaging.

Unlike conventional CT (computed tomography) systems – which combine X-ray measurements taken from different angles to produce a 3D image – photon-counting technology measures individual X-ray photons and their energy. This produces detailed, three-dimensional images that help clinicians to distinguish between different types of tissue and materials, better informing their decision making. As Dr John Carrino, a prominent musculoskeletal radiologist involved in clinical trials with MARS Bioimaging, notes: “Photon-counting CT is going to be the future of CT for medical imaging.”

Hydraulic brain: Body motion linked to fluid movement in the brain

The brain is more mechanically connected to the body than previously appreciated, scientists report in Nature Neuroscience. Through a study using mice and simulations, the team found a potential biological mechanism underlying why exercise is thought to benefit brain health: abdominal contractions compress blood vessels connected to the spinal cord and the brain, enabling the organ to gently move within the skull. This swaying facilitates the surrounding cerebrospinal fluid to flow over the brain, potentially washing away neural waste that could cause problems for brain function.

According to Patrick Drew, professor of engineering science and mechanics, of neurosurgery, of biology and of biomedical engineering at Penn State, the work builds on previous studies detailing how sleep and neuron loss can influence how and when cerebrospinal fluid flushes through the brain.

“Our research explains how just moving around might serve as an important physiological mechanism promoting brain health,” said Drew, corresponding author on the paper. “In this study, we found that when the abdominal muscles contract, they push blood from the abdomen into the spinal cord, just like in a hydraulic system, applying pressure to the brain and making it move.

Frontiers: Introduction:

Alzheimer’s disease, a progressive neurodegenerative disorder, is marked by beta-amyloid plaque accumulation and cognitive decline. The limited efficacy and significant side effects of anti-amyloid monoclonal antibody therapies have prompted exploration into innovative treatments like focused ultrasound therapy. Focused ultrasound shows promise as a non-invasive technique for disrupting the blood–brain barrier, potentially enhancing drug delivery directly to the brain and improving the penetration of existing therapeutic agents.

Mars dust storms are sparking electricity and rewriting the planet’s chemistry

Mars may look like a quiet, dusty world, but it’s actually buzzing with hidden electrical activity. Powerful dust storms and swirling dust devils generate static electricity strong enough to spark faint glowing discharges across the planet, triggering chemical reactions that reshape its surface and atmosphere. Scientists have now shown that these tiny lightning-like events can create a surprising mix of chemicals—including chlorine compounds and carbonates—and even leave behind distinct isotopic “fingerprints.”

Mars is often portrayed as a dry, lifeless desert, but it is far more active than it appears. Its thin atmosphere and dusty terrain create an environment where constant motion generates electrical energy. Dust storms and spinning dust devils sweep across the surface, continually reshaping the landscape and driving processes that scientists are only beginning to fully understand.

Planetary scientist Alian Wang has been studying this phenomenon in depth. In a series of studies, including recent work published in Earth and Planetary Science Letters, she has examined how these electrically charged dust activities influence the chemistry of Mars, particularly through their impact on isotopes.

Solar reactor uses old battery acid to turn plastic waste into clean hydrogen

Researchers have developed a solar-powered reactor to break down hard-to-recycle forms of plastic waste—such as drink bottles, nylon textiles and polyurethane foams—using acid recovered from old car batteries, and converting it into clean hydrogen fuel and valuable industrial chemicals. The results are reported in the journal Joule.

The reactor, developed by researchers from the University of Cambridge, is powered by the energy from the sun, and could be a cheaper, more sustainable alternative to current chemical-based recycling methods. The team says their method could create a circular system where one waste stream solves another.

Global plastic production is more than 400 million tons per year, yet only 18% is recycled. The rest is burned, landfilled, or leaks into ecosystems. The researchers believe that their method, known as solar-powered acid photoreforming, could become part of the solution to the global mountain of plastic waste.

Aquila Booster turns a weak pulsar into a powerhouse of PeV particles

A point-like cosmic particle accelerator pumps out PeV gamma rays stronger than expected from a pulsar 50x weaker than Crab.

What makes this discovery remarkable is not just the energy, but the efficiency. This system appears to convert energy into high-speed particles far more effectively than current physics says it should.

In simple terms, astronomers may have found a cosmic particle accelerator that outperforms even their best theoretical designs.

To understand the breakthrough, it helps to know what scientists were looking at. A pulsar wind nebula forms when a dead star, called a pulsar, spins rapidly and blasts out a stream of charged particles at nearly the speed of light.

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