CAR-T cell therapy is a last hope for many patients with blood, bone marrow or lymph gland cancer when other treatments are unsuccessful. A limiting factor of this 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.

An interdisciplinary research group combining mechanical engineering and biotechnology has taken up its work at the Institute for Molecular Systems Engineering and Advanced Materials (IMSEAM) of Heidelberg University. The team under the direction of Dr Kai Melde will pursue an innovative approach to biofabrication – 3D cell culture using ultrasound. Tools are being developed that can be used as an alternative to or enhancement for 3D printing.

Epigenetically active drugs enable the cell to read parts of the genome that were previously blocked and inaccessible. This leads to the formation of new mRNA transcripts and also new proteins, as scientists from the German Cancer Research Center and the University Hospital Tübingen have now published. These "therapy-induced epitopes" could help the immune system recognize cancer cells.

Epigenetically active drugs enable the cell to read parts of the genome that were previously blocked and inaccessible. This leads to the formation of new mRNA transcripts and also new proteins, as scientists from the German Cancer Research Center and the University Hospital Tübingen have now published. These "therapy-induced epitopes" could help the immune system recognize cancer cells.

A researcher team from Ecole Polytechnique Federal de Lausanne led by Dr. Vivek Thacker now group leader at the Department of Infectious Diseases at Heidelberg University Hospital have studied why tuberculosis bacteria form long strands and how this affects their infectivity. Their findings could lead to new therapies and have now been published in the journal Cell.

A phase I clinical trial is now starting at Tuebingen University Hospital in the Clinical Collaboration Unit (CCU) Translational Immunology, in collaboration with the Department of Internal Medicine I, which is investigating the therapeutic cancer peptide vaccine Fusion-VAC-XS15 in combination with immune checkpoint blockade by atezolizumab (Tecentriq®).

Tumor vaccines can help the body fight cancer. These vaccines alert the patient's immune system to proteins that are harbouring cancer-typical alterations. Physicians and cancer researchers from Heidelberg and Mannheim have now treated adult patients with advanced midline gliomas, difficult-to-treat brain tumors, with a peptide vaccine for the first time.

Current diagnostic methods do not always reliably distinguish between chronic inflammation of the pancreas and pancreatic cancer. About one third of all diagnoses are inconclusive. Scientists from the German Cancer Research (DKFZ) and from Heidelberg University Hospital (UKHD) therefore searched for molecular markers that could specify this diagnosis.

The computational design of new proteins for biomedical or other applications involves long computing times on powerful servers. A joint team of researchers from the Max Planck Institute for Biology Tübingen and the University Hospital Tübingen has now developed and tested a new computational method to greatly speed up the necessary energy calculations. Their framework allows for a precise and efficient design of functional proteins.

Scientists from the German Cancer Research Center (DKFZ) and the Cambridge Stem Cell Institute have developed an AI system that recognizes and characterizes white and red blood cells in microscopic images of blood samples. The algorithm can help physicians diagnose blood disorders and is available as an open source method for research purposes.

Germany has the most active market, Southern Europe wants more variety, and people in Poland find dairy substitutes too expensive, according to a recent study by the University of Hohenheim.

Known as the power plant of the cell, mitochondria are essential to human metabolism. Human mitochondria consist of 1,300 different proteins and two fatty biomembranes. The vast majority of mitochondrial proteins are produced with a cleavable transport signal and have to be actively transported into the mitochondria.

So far, 4.2 million animal tests under the REACH chemical regulation: A study from Konstanz and Baltimore quantifies the number of animals that died for the hazard assessment of chemicals in the chemical industry.

A new study published in Nature Medicine, July 2023 has identified two novel markers for screening high-grade squamous intraepithelial lesions (HSIL), a precursor to anal cancer, from the anal microbiome of people with HIV (PWH). PWH are at a significantly higher risk of developing anal cancer. Current screening methods, such as anal cytology, have low specificity for detecting HSIL, which hinders the prevention of anal cancer.

Wearable medical devices, such as soft exoskeletons that provide support for stroke patients or controlled drug delivery patches, have to be made of materials that can adapt intelligently and autonomously to the wearer's movements and to changing environmental conditions. These are the type of autonomously switchable polymer materials that have recently been developed by researchers at the University of Stuttgart and the University of…

The function of mast cells, which are part of the immune system, is still a mystery. Scientists at the German Cancer Research Center (DKFZ) have now shown in mice: mast cells function as a sensor that signals the animals to avoid antigens, including harmful allergens, and thereby protect themselves from health-threatening inflammatory reactions. The findings were published in the journal Nature.

Researchers from Konstanz and Zurich have deciphered a biochemical mechanism that ensures that newly formed proteins are processed correctly when they leave the cell's own protein factories. This solves a decade-old puzzle in protein sorting.

CureVac N.V. today announced that it has dosed the first patient with its investigational cancer vaccine CVGBM in a Phase 1 study. CVGBM is based on CureVac’s proprietary second-generation mRNA backbone and features a single mRNA, encoding eight epitopes derived from known tumor-associated antigens with demon­strated relevance in glioblastoma. A first data readout is expected in the second half of 2024.

In most cancers, it is not the growth of the primary tumor that determines the prognosis for the patient, but whether it will spread and form metastases. This process is very complex. There are often years between the development of the cancer and the aggressive growth of the metastases. Scientists from the DKFZ, the HI-STEM, the Ruhr University Bochum, Helmholtz Munich and ETH Zurich have studied and identified metastasis growth in breast cancer

Researchers at the Faculty of Medicine at the University of Freiburg have gained significant new insights into metabolic processes in the kidney. The scientists from the Institute of Genetic Epidemiology at the Medical Center - University of Freiburg measured tiny molecules, so-called metabolites, which occur in blood and urine and reflect our metabolism, in samples from more than 5,000 study participants.

Tübingen researchers describe connection between action and feeling of authorship - finding sheds light on delusions of external control in schizophrenia

Impaired function of lung fibroblast is considered causative for symptoms of the incurable lung disease COPD (Chronic Obstructive Pulmonary Disease). Using high-resolution epigenetic profiling, German and British scientists have now identified potential targets for COPD treatment. The team detected early epigenetic changes in the genome of COPD fibroblasts, providing new insights into the disease pathogenesis and potential therapeutic avenues.

Inflammatory fatty liver disease (NASH, non alcoholic steatohepatitis ) and the resulting liver cancer are driven by autoaggressive T cells. Scientists from the German Cancer Research Center (DKFZ) now show what ist behind this destructive behavior. In both mice and humans with NASH, they found increased numbers of activated B cells in the gastrointestinal tract.

Volkswagen Foundation to fund international research project with around 1.5 million euros. Interdisciplinary team led by the Institute for Global Health at Heidelberg University Hospital to research the transmission of pathogens from animals to humans in Thailand and Laos. Long-term goal is to develop sustainable preventive measures against future pandemics.

Centromeres, the DNA sections often found at the center of the chromosomes, display enormous interspecies diversity, despite having the same vital role during cell division across almost the entire tree of life. An international team of researchers has discovered that the variation in centromere DNA regions can be strikingly large even within a single species. The findings, now published in the journal Nature, shed light on the molecular…

Chronic myeloid leukemia (CML) is a type of blood cancer that arises from malignant changes in blood-forming cells of the bone marrow. It mainly occurs in older individuals and represents about 20 percent of all adult leukemia cases. A research team from the Institute of Molecular Medicine and Cell Research at the University of Freiburg has now demonstrated for the first time that mast cells play a crucial role in the development of CML.

The recently established ITCC-P4 gGmbH provides academic institutions and pharmaceutical companies with a comprehensive repertoire of modern laboratory models of pediatric tumors. The aim is to systematically test new treatment options for children and adolescents with cancer and to contribute data to regulatory approval processes in order to make the development of new cancer therapies for children and adolescents more attractive.

Optogenetic cell analysis - 15/05/2023

opto biolabs: how frustration and inventiveness led to the establishment of a company

When she found she had no suitable illumination devices for her doctoral thesis, Dr. Kathrin Brenker simply created her own customised adapters and founded a company called opto biolabs. Now, Brenker and company co-founder Luis Köbele sell two different types of devices. The main goal is to equip laboratories with illumination technologies that allow optogenetics methods to be used to accelerate development of optogenetic therapeutics.

Researchers at the University of Konstanz publish image analysis software that automatically detects and classifies defects of animal development. Thanks to artificial intelligence, "EmbryoNet" outperforms human experts in terms of speed, accuracy and sensitivity.

Initial Phase 1 part started with multivalent modified mRNA influenza vaccine candidates. Candidates developed in collaboration with GSK within broad infectious disease vaccine program encode for antigens covering four WHO-recommended flu strains.

Triple-negative breast cancer (TNBC) is the most aggressive and deadly form of breast cancer with limited treatment options. Tumor growth and relapse of TNBC are driven by breast cancer stem cells, and improved therapies that can eliminate those hardy cells are urgently needed. Researchers from the University of Frieburg discovered that coordinated differentiation and changes in the metabolism of breast cancer stem cells make them invisible for…

Konstanz researchers discover the function of a previously unexplored protein: In three characteristic steps, "C12orf29" links the ends of RNA strands. Proteins that perform this kind of RNA ligation were previously unknown in humans. The results of the study suggest that it is important for RNA repair during cellular stress.

How can camera images be used during minimally invasive surgeries to assess whether the operated organ is sufficiently perfused with blood? Scientists from the German Cancer Research Center (DKFZ) and the Städtisches Klinikum Karlsruhe have now succeeded in automatic monitoring of ischemia during a kidney surgery using only the optical properties of the tissue and not relying on injection of contrast agent.

Bacteria of the species Pseudomonas aeruginosa are antibiotic-resistant hospital germs that can enter blood, lungs and other tissues through wounds and cause life-threatening infections. In a joint project, researchers from the Universities of Freiburg and Strasbourg in France have discovered a mechanism that likely contributes to the severity of P. aeruginosa infections.

Patients have 30 percent fewer serious side effects when medication doses are tailored to their genetic profile. This is what an international research consortium has found out, including the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology at the Bosch Health Campus. With an individual DNA medication pass, as used in the study, treatments can be made more effective and safer in the future.

Cancer immunotherapies often fail because the immune cells are paralysed by immunosuppressive conditions in the tumor. Scientists from Heidelberg, Mannheim and Tel Aviv have now shown on tissue samples from patients as well as on tumor models in mice that the functionality of the immune defence depends decisively on certain helper cells.

Heidelberg scientists succeed in boosting the efficiency of CRISPR/Cas9 and related methods and modifying initially inaccessible DNA sequences.

With the "Česká Hlava" awards, the Czech government has been honoring the country's most brilliant minds every year since 2002 and recognizing exceptional achievements in research, development and innovation. Martina Benešová-Schäfer of the German Cancer Research Center was among the six laureates honored in 2022 at Charles University in Prague.

Acute Graft-versus-host disease (GvHD) is a life-threatening complication after leukemia treatment with allogeneic stem cell transplantation i.e. the transplantation of cells from another person. GvHD occurs when the transplanted immune cells are overly active and damage the receiving patient's healthy tissue. Researchers found that an endogenous molecule can mitigate this misdirected immune response.

The hospital pathogen Pseudomonas aeruginosa requires the sugar-binding proteins LecA and LecB to form biofilms as well as to attach to and penetrate host cells. These so-called lectins are therefore suitable targets for active substances to combat Pseudomonas infections. Researchers from Saarbrücken and Freiburg have now produced potent inhibitors for LecA and LecB that are more stable and soluble than previous drug candidates.

Researchers at the University of Freiburg Medical School led by Prof. Dr. Johannes Letzkus and the Max Planck Institute for Brain Research have discovered that a little-studied area of the brain, the "zone of uncertainty" or "zona incerta," communicates with the neocortex in unconventional ways to rapidly control memory formation.

Using new microscopic methods in combination with machine learning-based image analysis, researchers from Freiburg have discovered new structures on the surface of living B cells that affect the distribution and possibly the function of their antigen receptors. The researchers' study has been published in The EMBO Journal.

CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid (“mRNA”), today announced positive preliminary data from ongoing Phase 1 clinical programs in COVID-19 and seasonal flu, assessing both modified and unmodified mRNA technology. The tested vaccine candidates are being developed in collaboration with GSK.

Mitochondria are considered to be the power plants of cells and are essential for human metabolism. Dysfunction in 40 percent of mitochondrial proteins are associated with human diseases, which is why mitochondria also play an important role in medical research. A previously unexplained process in the complex mitochondria was the formation of their barrel pores.

In our bones, specialized cells called osteoblasts are responsible for building up bone substance. A team of researchers led by scientists from the DKFZ-Hector Cancer Institute at the University Medical Center Mannheim* and the University Medical Center Hamburg Eppendorf has now identified an enzyme that controls the activity of osteoblasts.

Heidelberg scientists decode the genetic foundations of rapid testicle evolution in mammals and humans. Evolutionary pressure across male mammals to guarantee the procreation of their own offspring led to a rapid evolution of the testicle.

Inhibition of a protein complex in cells of the immune system prevents rejection of transplanted organs – this has been shown in a study by immunologists from the University of Konstanz, the Biotechnology Institute Thurgau (BITg) and Chongqing Cancer University Hospital.

Neurodegenerative diseases - 12/12/2022

Blood-based biomarkers allow the early prediction of Alzheimer's risks

Most dementia diseases develop insidiously and are only detected at an advanced stage. Researchers at the University of Heidelberg and the German Cancer Research Center (DKFZ) have now identified the glial fibre acidic protein (GFAP) in the blood as a promising biomarker that can be used to determine an increased risk of developing Alzheimer's disease up to 17 years before diagnosis.

During infections, the hematopoietic system switches from normal to emergency mode. This improves the defense against the pathogens. Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now found an epigenetic switch in blood stem cells and progenitor cells of mice that can trigger the switch from one mode to the other.

The newborn's immune system is suddenly confronted with microorganisms, food and numerous environmental influences at birth. How do the baby's immune cells prepare for this moment during pregnancy and birth? How do external influences shape the immune system immediately after birth? And what influence does an event like a premature birth have?

The Bundesanstalt für Materialforschung und -prüfung (BAM) is developing a more sustainable process to produce active pharmaceutical ingredients in a major EU project: The pilot project is intended to demonstrate the advantages of mechanochemistry for more environmentally friendly and CO2-neutral pharmaceutical production.

Researchers of the University of Freiburg introduce biosensor for the nucleic acid amplification-free detection of SARS-CoV-2 RNA.

DZNE researchers discover link between the protein medin and Alzheimer's disease. The protein medin is deposited in the blood vessels of the brains of Alzheimer's patients along with the protein amyloid-β. DZNE Researchers have discovered this so-called co-aggregation. They have now published their observation in the renowned journal Nature.

Using animal-free methods to assess the hazard potential of chemicals to the nervous system of unborn children? An international research team including toxicologists from Konstanz and Düsseldorf has developed a testing battery based on human cells that has the potential to replace traditional methods for assessing developmental neurotoxicity.

Researchers have created a tool that maps how breast cancer grows in previously unseen detail, and highlights how the cells around the tumour may be the key to controlling the spread of disease. The new technology can trace which populations of breast cancer cells are responsible for the spread of the disease, and for the first time highlights how the location of cancer cells could be as important as mutations in tumor growth The new study is…

The health of nerve cells is closely linked to the auxiliary cells that surround them, the so-called glial cells. It still remains largely unknown what role glial cells play in age-related diseases.

During the growth and development of living organisms, different types of cells must come into contact with each other in order to form tissues and organs together. A small team working with Prof. Dr. Anne Classen of the Excellence Cluster CIBSS of the University of Freiburg has discovered that complex changes in form, or morphogenesis, during development are driven exclusively via the affinity of cells to each other.

Toxicologists from the University of Konstanz have found that the protein p53 continuously protects our cells from tumorigenesis by coordinating important metabolic processes that stabilize their genomes.

Why do metastases often only appear after the original tumor has been surgically removed? Scientists from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the Mannheim Medical Faculty of Heidelberg University have now published an explanation for this phenomenon. They were able to identify a messenger substance of the cancer cells that locally promotes the growth of the primary tumor.

Researchers of the University of Freiburg have discovered a previously unknown function of septins in defending cells against dangerous hospital pathogens.

Apogenix, a biopharmaceutical company developing next generation immunotherapeutics, announced today that asunercept showed statistically significant benefits for hospitalized COVID-19 patients in the ASUNCTIS trial. The open-label multi-center phase II trial investigated efficacy and safety of asunercept in 435 patients with moderate to severe COVID-19 disease.

Researchers from Freiburg and Harvard publish the three-dimensional structure of the B cell antigen receptor, shedding new light on its composition.

Dossier - 12/10/2022

The health sector must become greener

Worldwide, the health sector is struggling with the consequences of global warming, but fatally is itself responsible for a significant proportion of greenhouse gas emissions. Studies show that hospitals and rehabilitation clinics in particular have great potential for reducing these emissions and, like the manufacturing industry, need to fundamentally revise established processes.

In the brain of adult mammals neural stem cells ensure that new nerve cells, i.e. neurons, are constantly formed. This process, known as adult neurogenesis, helps mice maintain their sense of smell. A research team led by Dr Francesca Ciccolini at the Interdisciplinary Center for Neurosciences (IZN) of Heidelberg University recently discovered a second stem cell population in the mouse brain.

Although just cute little creatures at first glance, the microscopic geckos and octopuses fabricated by 3D laser printing in the molecular engineering labs at Heidelberg University could open up new opportunities in fields such as microrobotics or biomedicine. The printed microstructures are made from novel materials – known as smart polymers – whose size and mechanical properties can be tuned on demand and with high precision.

Screening trials for the early detection of rare diseases often fail due to insufficient predictive power of the results. For the rare HPV-related cancer of the pharynx, scientists from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) now relied on the combined detection of antibodies against two different viral proteins in a proof-of concept trial.

Cancer cells often grow in environments that are low in nutrients, and they cope with this challenge by switching their metabolism to using proteins as alternative "food". Building on genetic screens, an international team of scientists could identify the protein LYSET as part of a pathway that allows cancer cells to make this switch. Their findings are now published in the journal Science.

Tuberculosis is one of the leading causes of death worldwide, with an estimated 1.4 million deaths and ten million people infected annually. Resistant and multidrug-resistant (MDR) variants of the tuberculosis pathogen Mycobacterium tuberculosis pose a major threat to tuberculosis control and global health.

Changes known as epigenetic modifications play an important role in cancer development, among other things. Being able to analyze them quickly and reliably could, for example, contribute significantly to the further development of personalized therapy.

CureVac N.V., a global biopharmaceutical company developing a new class of transformative medicines based on mRNA, today announced the start of a Phase 1 study of the modified COVID-19 mRNA vaccine candidate CV0501, administered as a booster dose to previous COVID-19 vaccination. Developed in collaboration with GSK, CV0501 is based on CureVac’s second-generation mRNA backbone and is designed to specifically protect against the Omicron variant.

University of Tübingen team discovers how malformations of the blood vessels can occur in mice – yielding information with possible ramifications for retinal disease.

Mitochondria are the power plants of cells, and they contain their own genetic material and RNA molecules. Scientists from the German Cancer Research Center (DKFZ) have now discovered that certain modifications in mitochondrial RNA boost the invasive spread of cancer cells by supporting protein synthesis in mitochondria.

Does COVID-19 vaccination increase the risk of cancer patients undergoing therapy with immune checkpoint inhibitors to suffer a dangerous immune complication known as a "cytokine release syndrome"? A team of Heidelberg physicians and scientists has now shown in a clinical study: Increased serum levels of the characteristic cytokines occur frequently in cancer patients, but clinically relevant cases of the dreaded syndrome were not…

Assay to support the diagnosis of autoimmune diseases - 22/06/2022

Tracking down pathogenic immune complexes

Soluble complexes of antibodies and their target structures circulating in the blood can trigger serious systemic inflammations. Dr. Philipp Kolb and Haizhang Chen from the Institute of Virology at the Freiburg University Medical Centre have developed a sensitive, cell-based test system for detecting these immune complexes. The system can be used to diagnose systemic autoimmune diseases, and also severe cases of COVID-19.

Scientists from the 2. Physics Institute at the University of Stuttgart and the Max Planck Institute for Medical Research were now able to take the next step towards synthetic cells: They introduced functional DNA-based cytoskeletons into cell-sized compartments and showed functionality. The results were recently published in Nature Chemistry.