Improving the efficacy of cancer immunotherapy with modified CAR-T cells

Water color art illustrates the publication by Velasco et al. The authors systematically engineered novel Chimeric Antigen Receptors (CARs), each containing one of the signaling chains of the natural T cell receptor: epsilon, gamma, delta and zeta (from left to right, from top to bottom) to create innovative CAR T cells. The work demonstrated that each signaling chain imprints the functioning of the CAR T cells (represented by the different colors) impacting thus their anti-tumor activity.
Illustration Credit: Sara Wossning Minguet

CAR-T cell therapy is a last hope for many patients with blood, bone marrow or lymph gland cancer when other treatments such as chemotherapy are unsuccessful. A limiting factor of this otherwise very effective and safe therapy is that the cells used in the process quickly reach a state of exhaustion. Researchers at the University of Freiburg have now been able to prevent this exhaustion and thus significantly improve the effect of the therapy in a preclinical animal model. The new results have been published in the journal Nature Immunology.

Using the body’s own defenses against cancer

CAR-T cells are one of the personalized cancer therapies and have been used in specialized centers in Europe since 2018. In this complex treatment, immune cells, or more precisely T cells, are taken from the blood of cancer patients, genetically engineered in the laboratory with a chimeric antigen receptor (CAR) and then re-administered. The receptor helps the T cells to identify and kill cancer cells. As a result, the therapy utilizes the body’s own cells to permanently eradicate the cancer.

Parkinson's: New hope when treatment options seem exhausted

Prof. Paul Lingor
Photo Credit: Courtesy of Technical University of Munich

As Parkinson's progresses, more invasive therapies are used that require brain surgery, for example. When these no longer deliver the desired results, physicians often conclude that treatment options are exhausted. A study led by researchers at the Technical University of Munich (TUM) now shows that such patients can still benefit from a change in treatment. So far, however, this option has only been used very rarely.

A team led by Prof. Paul Lingor has examined data from 22 German Parkinson's centers. The result: although there are several options for therapies in the late stages of the disease, rarely is more than one used - although those affected often benefit from them.

Parkinson's disease is the world’s second-most common neurodegenerative disease after Alzheimer's. So far it has proved incurable. Only the symptoms can be treated. In the early stages, tablets can generally provide relief from complaints. As the disease progresses, this is often no longer enough.

Phytoplankton uptake of methylmercury is controlled by thiols

In the sea, phytoplankton are the first step when methylmercury is absorbed into the food web. The image was taken under a microscope and shows a spring bloom of phytoplankton in the Bothnian Sea.
 Image Credit: Marlene Johansson

Methylmercury is one of the chemicals that poses the greatest threat to global public health. People ingest methylmercury by eating fish, but how does the mercury end up in the fish? A new study shows that the concentrations of so-called thiols in the water control how available methylmercury is to living organisms.

For methylmercury to enter the food web, it must be absorbed from the water by organisms and the uptake takes place primarily by phytoplankton. This results in a dramatic enrichment, where the levels of methylmercury can increase by a factor of 10,000 to 100,000. However, there is a great deal of variation between different aquatic environments, and it has so far been unclear what controls the process and why the variation is so large.

Higher risk of 17 cancers after high BMI in late teens

Aron Onerup, Institute of Clinical Sciences, and Maria Åberg, Institue of Medicine, Sahlgrenska Academy at the University of Gothenburg.
Photo Credit: Anna Onerup, Johan Wingborg

Men who are overweight or obese at age 18 have a higher risk of 17 different cancers later in life. This has been shown in a study at the University of Gothenburg. The research also describes how the youth obesity epidemic is expected to affect the cancer situation over the next 30 years.

In August, a study on higher cancer risk in men who had lower aerobic fitness recorded at the time of compulsory conscription for military service at the age of 18 was presented. The results were independent of any overweight or obesity at conscription.

In two new studies published in the journals Obesity and Cancer Medicine, the same research team is now focusing on body mass index (BMI), while the results are independent of the participants' aerobic fitness level. And it turns out that higher BMI at age 18 can be linked to even more cancers later in life than poor fitness at the same age.

High BMI at conscription was associated with a higher risk of 17 cancers: lung, head and neck, brain, thyroid, esophageal, stomach, pancreatic, liver, colon, rectal, kidney, and bladder cancer, as well as malignant melanoma, leukemia, myeloma, and lymphoma (both Hodgkin's and non-Hodgkin's).

Mystery Resolved: Black Hole Feeding and Feedback at the Center of an Active Galaxy

Fig. 1
An illustration depicting the distribution of interstellar medium in the active galactic nucleus based on the results of this observation.
Illustration Credit: ©ALMA (ESO/NAOJ/NRAO), T. Izumi et al.

An international research team led by Takuma Izumi, an assistant professor at the National Astronomical Observatory of Japan, has observed in high resolution (approximately 1 light year) the active galactic nucleus of the Circinus Galaxy - one of the closest major galaxies to the Milky Way. The observation was made possible by the Atacama Large Millimeter/Submillimeter Array (ALMA) astronomical observatory in Chile.

This breakthrough marks the world's first quantitative measurement at this scale of gas flows and their structures of a nearby supermassive black hole in all phase gases, including plasma, atomic, and molecular. Such high resolution allowed the team to team to capture the accretion flow heading towards the supermassive black hole, revealing that this accretion flow is generated by a physical mechanism known as 'gravitational instability.' Furthermore, the team also found that a significant portion of this accretion flow does not contribute to the growth of the black hole. Instead, most of the gas is expelled from the vicinity of the black hole as atomic or molecular outflows, and returns to the gas disk to participate again into an accretion flow towards the black hole, much like how water gets recycled in a water fountain. These findings represent a crucial advancement towards a greater understanding of the growth mechanisms of supermassive black holes.

Nanosatellite to Test Novel AI Technologies

Image Credit: Julius-Maximilians-Universität Würzburg

A new Würzburg space mission is on the home straight: The SONATE-2 nanosatellite will test novel artificial intelligence hardware and software technologies in orbit.

After more than two years of development, the nanosatellite SONATE-2 is about to be launched. The lift-off into orbit by a rocket is expected in March 2024. The satellite was designed and built by a team led by aerospace engineer Professor Hakan Kayal from Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany.

JMU has been developing small satellite missions for around 20 years. SONATE-2 now marks another high point.

The satellite will test novel artificial intelligence (AI) hardware and software technologies in near-Earth space. The goal is to use it to automatically detect anomalies on planets or asteroids in the future. The Federal Ministry of Economic Affairs is funding the project with 2.6 million euros.

Potential inheritable effects and ethical considerations of epigenome editing

Illustration Credit: Courtesy of Institute for the Advanced Study of Human Biology

Epigenome editing is an emerging technology used to regulate gene function by controlling epigenetic states at specific locations on the genome. This method is distinct from traditional genetic editing, which involves permanently altering the DNA sequence. Notably, the intervention effects of epigenome editing are thought to be reversible, making this technology particularly attractive for its potential therapeutic applications in the treatment of genetic disorders and chronic diseases. Although some researchers argue that it presents fewer ethical issues compared with permanent genome editing, especially in terms of its impact on offspring, the potential for transgenerational epigenetic inheritance has also been reported, suggesting that epigenetic changes could be inherited across generations in mammals. This study sought to examine the ethical and practical questions of epigenome editing and its use for therapeutic purposes, especially in the context of transgenerational epigenetic inheritance and the potential consequences for future generations.

Urbanization threatens ecological health of South China’s Greater Bay Area

Photo Credit: Professor Joe Lee Shing-yip

Rapid urbanization in South China’s Greater Bay Area poses a significant threat to the ecological well-being of Deep Bay and its surrounding wetlands, new research shows.

The study, by the Chinese University of Hong Kong (CUHK) and the University of Exeter, highlights the urgent need to address the impact of urbanization on the region’s fragile coastal wetland ecosystems, especially their vital role in supporting migratory waterbirds.

It focused on Deep Bay, in the Pearl River estuary, which plays a crucial role as a refueling ground for migratory waterbirds along the East Asian-Australasian Flyway.

The team analyzed long-term environmental data spanning over 40 years to reveal the alarming consequences of dramatic changes.

They revealed a 30% decline in various water bodies such as mudflats, fishponds and geiwais (shallow ponds found in mangrove areas) between 1988 and 2020. Simultaneously, there was a 15.6 km2 increase in impervious surface coverage, primarily due to the conversion of fishponds and wetlands into concrete structures.

New study findings call into question the superiority of stem cell therapy for treating knee pain

Image Credit: rawpixel

Characterized by extensive damage to joints and debilitating pain, osteoarthritis (OA) impacts millions of people worldwide and has long posed a substantial clinical and economic burden.

In spite of advances in diagnosis, medications, and short-term pain management solutions, the elusive goal of a disease-modifying OA drug has remained out of reach. In recent years though, the use of stem cell therapy has gained traction as a promising alternative to surgery and for improving patients’ quality of life.  

Through a grant from the Marcus Foundation, an Emory team of investigators in collaboration with other recruitment sites throughout the nation explored the potential of mesenchymal stem cells as a game-changing treatment option for knee OA, one of the most common causes of chronic knee pain. This type of treatment seeks to harness the ability of a patient’s own cells to repair damaged tissue. However, the availability of robust data from well-designed randomized controlled trials has been limited, particularly in comparison to the gold-standard of treatment for knee OA, corticosteroid injections (CSI).

Molecular blueprint of circuits governing locomotor speed

Zebra fish
Photo Credit: Lars Bräutigam

Researchers at Karolinska Institutet, Sweden have uncovered the molecular logic underpinning the assembly of spinal circuits that control the speed of locomotion in adult zebrafish. The study has recently been published in Nature Neuroscience.

What does the study show?

A fundamental hallmark of motor actions is the flexibility of their timing, speed and strength that is central to rapid adaptation to the ever-changing world around us. This is particularly apparent during locomotion, a behavior that involves full-body coordination characterized by sudden changes in speed and strength.

“In this study, we used single-cell RNA sequencing in adult zebrafish to link the molecular diversity of motoneurons and interneurons with their modular circuit organization that is responsible for changes in locomotor speed” says Abdel El Manira, Professor at the Department of Neuroscience at Karolinska Institutet, and corresponding author of the article.