Epifadin from the nasal microbiome - 28/03/2024 From the nose: novel antibiotic substance discovered Antibiotics are becoming an increasingly blunt weapon against infectious diseases. The number of (multi-)resistant germs has been rising rapidly for years and even reserve antibiotics no longer work. Researchers at the University of Tübingen have now isolated a completely new antibiotic substance called epifadin from the microbiome of the human nose. It is effective against many different bacteria - including the dangerous hospital MRSA.https://www.gesundheitsindustrie-bw.de/en/article/news/nose-novel-antibiotic-substance-discovered
Press release - 27/03/2024 Heidelberg Pharma granted orphan drug designation by FDA for its proprietary ATAC candidate HDP-101 Heidelberg Pharma AG (FSE: HPHA), a clinical stage biotech company developing innovative Antibody Drug Conjugates (ADCs), is pleased to announce that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for the treatment of multiple myeloma to its lead candidate HDP-101. Heidelberg Pharma is investigating the candidate in a clinical Phase I/IIa study for the treatment of relapsed/refractory multiple myeloma (RRMM).https://www.gesundheitsindustrie-bw.de/en/article/press-release/heidelberg-pharma-granted-orphan-drug-designation-fda-its-proprietary-atac-candidate-hdp-101
Press release - 14/03/2024 Next milestone in the treatment of liver tumors and acute and chronic liver diseases The results of a Tuebingen-led study raise hope that a newly developed drug could herald a new era in oncological liver surgery and transplantation. The drug could even have the potential to significantly improve the treatment of acute and chronic liver diseases. The drug candidate "HRX-215" is a so-called MKK4 inhibitor, i.e. the drug inhibits the MKK4 protein found in liver cells and thus leads to an increase in the regeneration of…https://www.gesundheitsindustrie-bw.de/en/article/press-release/next-milestone-treatment-liver-tumors-and-acute-and-chronic-liver-diseases
Press release - 02/02/2024 Epigenetic status determines metastasis Scientists from the German Cancer Research Center (DKFZ) and Medical Faculty Mannheim of the Heidelberg University investigated in mice how spreading tumor cells behave at the site of metastasis: Some tumor cells immediately start to form metastases. Others leave the blood vessel and may then enter a long period of dormancy. What determines which path the cancer cells take is their epigenetic status. https://www.gesundheitsindustrie-bw.de/en/article/press-release/epigenetischer-status-entscheidet-ueber-metastasierung
Funding EU Joint Programme - Neurodegenerative Disease Research (JPND): Mechanisms and measurement of disease progression in the early phase of neurodegenerative diseases Funding programme, Funded by: EU JPND I BMBF, sb_search.searchresult.label.programSubmissionDate: 05/03/2024 https://www.gesundheitsindustrie-bw.de/en/database/funding/eu-joint-programme-neurodegenerative-disease-research-jpnd-mechanisms-and-measurement-disease-progression-early-phase-neurodegen
Press release - 31/01/2024 Precursor of Cholesterol Protects Cancer Cells From Cell Death and Makes them Aggressive A precursor of cholesterol can protect cancer cells from a form of cell death known as ferroptosis. Scientists of the University of Würzburg, the German Cancer Research Center (DKFZ), and the Stem Cell Institute HI-STEM* published this finding in the journal Nature. The results opens up exciting prospects for further improving the treatment of cancer and other diseases associated with oxidative stress and ferroptosis.https://www.gesundheitsindustrie-bw.de/en/article/press-release/cholesterin-vorstufe-schuetzt-krebszellen-vor-zelltod-und-macht-sie-aggressiver
Health Data Futures project - 11/01/2024 Creating a network of trust In the three-nation project "Health Data Futures", stakeholders and experts from Germany, France and Switzerland have launched a series of patient-centred innovations. Using various future scenarios, the project partners may be able to come up with even more scenarios.https://www.gesundheitsindustrie-bw.de/en/article/news/creating-network-trust
Press release - 03/01/2024 Reprogrammed fat cells support tumor growth Mutations of the tumor suppressor p53 not only have a growth-promoting effect on the cancer cells themselves, but also influence the cells in the tumor's microenvironment. Scientists at the Weizmann Institute in Israel and at the German Cancer Research Center (DKFZ) have now shown that p53-mutated mouse breast cancer cells reprogram fat cells.https://www.gesundheitsindustrie-bw.de/en/article/press-release/reprogrammed-fat-cells-support-tumor-growth
Press release - 18/12/2023 Researchers discover novel antibiotic substance from the human nose For the first time, the active substance epifadin has been isolated at the University of Tübingen – Epifadin is produced by specific bacteria in the nose and on the skin of humans, has an antibiotic effect, and is the first example of a previously unknown antimicrobial compound class.https://www.gesundheitsindustrie-bw.de/en/article/press-release/researchers-discover-novel-antibiotic-substance-human-nose
Funding NutriBrain: Modulation of brain ageing through nutrition and healthy lifestyle Funding programme, Funded by: ISCIII & BMBF, sb_search.searchresult.label.programSubmissionDate: 15/01/2024 https://www.gesundheitsindustrie-bw.de/en/database/funding/richtlinie-zur-foerderung-von-transnationalen-forschungsprojekten-zur-modulation-der-alterung-des-gehirns-durch-ernaehrung-und-e
Augmented reality for visual orientation - 15/11/2023 Fall prevention with the help of balance-enhancing AR glasses As we age, our eyesight deteriorates and we have increasing difficulties with orientation. This can lead to balance problems and fatal falls. A team led by Dr. Lorenz Assländer from the University of Konstanz is currently developing a prototype of augmented reality (AR) glasses that use superimposed patterns to facilitate visual orientation in space, thereby helping to improve balance control and prevent falls.https://www.gesundheitsindustrie-bw.de/en/article/news/fall-prevention-help-balance-enhancing-ar-glasses
Press release - 06/11/2023 Improving the efficacy of cancer immunotherapy with modified CAR-T cells 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/improving-efficacy-cancer-immunotherapy-modified-car-t-cells
Press release - 07/08/2023 Vegan trend in Europe: In Germany, milk substitutes from plants are most popular alternative 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/vegan-trend-europe-germany-milk-substitutes-plants-are-most-popular-alternative
Project BlindZero - 03/08/2023 Hope for patients with eye diseases: human cornea from 3D printers Thousands of cornea transplants are performed every year. However, donors are rare and the procedure is not always without complications. Researchers at the University of Heidelberg are developing an innovative technique in the project BlindZero. It involves ‘printing’ human corneas directly onto patients’ eyes using 3D bioprinting. The reprogrammed genetically engineered cells used for this purpose are not expected to cause a rejection reaction.https://www.gesundheitsindustrie-bw.de/en/article/news/hope-patients-eye-diseases-human-cornea-3d-printers
Press release - 20/07/2023 Anal Cancer Screening: New Microbiome-Associated Biomarkers Could Improve Prevention 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/anal-cancer-screening-new-microbiome-associated-biomarkers-could-improve-prevention
Press release - 12/07/2023 Mast cells as a sensor: Enigmatic immune cells help to avoid harmful allergens 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/mastzellen-als-sensor-raetselhafte-immunzellen-helfen-schaedliche-allergene-zu-vermeiden
Press release - 23/06/2023 The molecular control centre of our protein factories 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/molecular-control-centre-our-protein-factories
Press release - 16/06/2023 What determines whether breast cancer cells can form metastases? 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 cancerhttps://www.gesundheitsindustrie-bw.de/en/article/press-release/what-determines-whether-breast-cancer-cells-can-form-metastases
Reduced immunosuppression possible in transplantations - 05/06/2023 Modified immune cells produce donor-specific tolerance Traditionally, transplant recipients have had to take immunosuppressive medication for life to prevent organ rejection. However, there are considerable side effects involved. Using modified immune cells (MICs), TolerogenixX GmbH from Heidelberg has now managed to generate donor-specific tolerance in recipients of living kidney transplants without suppressing the overall immune system.https://www.gesundheitsindustrie-bw.de/en/article/news/modified-immune-cells-produce-donor-specific-tolerance
Press release - 23/05/2023 B cells promote liver cancer with dangerous dual strategy 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/b-cells-promote-liver-cancer-dangerous-dual-strategy
Press release - 22/05/2023 Prevention of pandemics 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/prevention-pandemics
Press release - 01/03/2023 Pseudomonas aeruginosa Bacteria produce a molecule that paralyzes immune system cells 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/pseudomonas-aeruginosa-bakterien-stellen-ein-molekuel-her-das-zellen-des-immunsystems-laehmt
Press release - 07/02/2023 Hertie Foundation establishes new institute combining artificial intelligence and neuroscience This month marks the launch of an outstanding project integrating artificial intelligence (AI) and neuromedicine – the Hertie Institute for Artificial Intelligence in Brain Health (Hertie AI). Founded on February 1 at the Medical Faculty of the University of Tübingen, it will be the first institute in Germany to research the prevention and early diagnosis of diseases of the nervous system using artificial intelligence methods.https://www.gesundheitsindustrie-bw.de/en/article/press-release/hertie-stiftung-gruendet-neues-institut-das-kuenstliche-intelligenz-und-neurowissenschaften-verbindet
Press release - 06/02/2023 Fewer side effects thanks to personalised medicine 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/weniger-nebenwirkungen-dank-personalisierter-medizin
Press release - 31/01/2023 ERC Consolidator Grants for Two Researchers from KIT In the 2022 allocation round for the award of the prestigious Consolidator Grants of the European Research Council, researchers of Karlsruhe Institute of Technology (KIT) have been successful. For their projects in the fields of photovoltaics and medical sensor technology, physicist Ulrich W. Paetzold and chemist Frank Biedermann will receive approximately two million euros over the next five years.https://www.gesundheitsindustrie-bw.de/en/article/press-release/erc-consolidator-grants-fuer-zwei-forscher-des-kit
Press release - 24/01/2023 What keeps the immune defense in brain tumors functional 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/was-die-abwehrzellen-hirntumoren-funktionsfaehig-haelt
Press release - 17/01/2023 Endogenous molecule protects from life-threatening complications after stem-cell transplantation 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/koerpereigenes-molekuel-schuetzt-vor-lebensbedrohlichen-komplikationen-nach-stammzelltransplantation
Press release - 17/01/2023 Sugar-based inhibitors disarm the pathogen Pseudomonas aeruginosa 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/zuckerbasierte-inhibitoren-entwaffnen-den-krankheitserreger-pseudomonas-aeruginosa
Press release - 11/01/2023 Newly discovered surface structures may affect immune function 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/newly-discovered-surface-structures-may-affect-immune-function
Funding IHI call 3 Funding programme, Funded by: European Union, sb_search.searchresult.label.programSubmissionDate: 15/03/2023 https://www.gesundheitsindustrie-bw.de/en/database/funding/ihi-call-3
Press release - 20/12/2022 Rapid Evolution of Spermatogenesis 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. https://www.gesundheitsindustrie-bw.de/en/article/press-release/rapid-evolution-spermatogenesis
Press release - 20/12/2022 New approach prevents rejection of transplanted organs 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/new-approach-prevents-rejection-transplanted-organs
Funding EU4Health Programme (EU4H) – Action Grants 2022 Funding programme, Funded by: European Union, sb_search.searchresult.label.programSubmissionDate: 21/02/2023 https://www.gesundheitsindustrie-bw.de/en/database/funding/eu4health-programme-eu4h-action-grants-2022
Press release - 01/12/2022 Development of the immune system before and after birth 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?https://www.gesundheitsindustrie-bw.de/en/article/press-release/development-immune-system-and-after-birth
Press release - 29/11/2022 Prototype funding for two Konstanz projects Chemical building blocks from plastic waste; Reducing the risk of falls using virtual orientation aids: Konstanz chemists Manuel Häußler and Lukas Odenwald as well as sport scientist Lorenz Assländer receive Baden-Württemberg prototype funding for their transfer projects "Waste2DCA" and "Augmented Balance".https://www.gesundheitsindustrie-bw.de/en/article/press-release/doppelter-erfolg-der-prototypenfoerderung
Start-up Actimi GmbH - 23/11/2022 Real-time telemonitoring of heart failure Improved quality of life for patients and lower costs for health insurers: these are the advantages of telemonitoring patients with advanced heart failure. The Stuttgart-based start-up Actimi offers an all-in-one platform for those who treat and those who suffer from the disease.https://www.gesundheitsindustrie-bw.de/en/article/news/real-time-telemonitoring-heart-failure
Press release - 17/11/2022 New target for Alzheimer's therapies found 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/new-target-alzheimers-therapies-found
Press release - 09/11/2022 New Molecular Microscopy Uncovers how Breast Cancer Spreads 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…https://www.gesundheitsindustrie-bw.de/en/article/press-release/new-molecular-microscopy-uncovers-how-breast-cancer-spreads
Press release - 02/11/2022 The guardian of the (epi-)genome 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/guardian-epi-genome
Press release - 20/10/2022 Cytoskeleton acts as cells’ bouncer for bacteria Researchers of the University of Freiburg have discovered a previously unknown function of septins in defending cells against dangerous hospital pathogens.https://www.gesundheitsindustrie-bw.de/en/article/press-release/das-zellskelett-haelt-die-eintrittspforte-fuer-bakterien-geschlossen
Press release - 19/10/2022 Apogenix’ Asunercept Demonstrates Efficacy in Phase II Trial for the Treatment of Hospitalized COVID-19 Patients 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/apogenixs-asunercept-zeigt-wirksamkeit-phase-ii-studie-zur-behandlung-von-covid-19-patienten-im-krankenhaus
Press release - 19/10/2022 Molecular structure of one of the most important receptors in the immune system unraveled Researchers from Freiburg and Harvard publish the three-dimensional structure of the B cell antigen receptor, shedding new light on its composition.https://www.gesundheitsindustrie-bw.de/en/article/press-release/molecular-structure-one-most-important-receptors-immune-system-unraveled
Press release - 05/10/2022 Second Stem Cell Type Discovered in Mouse Brain 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. https://www.gesundheitsindustrie-bw.de/en/article/press-release/zweiter-stammzelltyp-im-maeusehirn-entdeckt
Press release - 01/09/2022 Personalised antibiotic treatment strategies for tuberculosis patients 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.https://www.gesundheitsindustrie-bw.de/en/article/press-release/personalisierte-antibiotika-behandlungsstrategie-bei-tuberkulose-erkrankten
Press release - 03/06/2022 Deep Learning helps improve gene therapies and antiviral drugs The nuclease Cas13b associated with the CRISPR gene scissors, which is an enzyme that degrades nucleic acids, has the potential to be used in the future in hereditary diseases to switch off unwanted genes. In the fight against infections, this nuclease is also being researched as an antiviral agent, as Cas13b can specifically intervene in the genetic material of viruses and render them harmless.https://www.gesundheitsindustrie-bw.de/en/article/press-release/deep-learning-helps-improve-gene-therapies-and-antiviral-drugs
Press release - 12/05/2022 New hope for broad spectrum viral entry inhibitors – Negatively charged polymer proves effective against a wide range of viruses While broad-spectrum antibiotics can offer protection against a wide variety of bacteria, there are currently no analogous clinically available broad-spectrum antiviral agents that can act on several different viruses. An international research team has now shown that polystyrene sulfonate (PSS), a negatively charged polymer, has the potential to be used in the prevention of viral infections – not only in the fight against the SARS-CoV-2 and cold…https://www.gesundheitsindustrie-bw.de/en/article/press-release/new-hope-broad-spectrum-viral-entry-inhibitors-negatively-charged-polymer-proves-effective-against-wide-range-viruses
Press release - 28/04/2022 Tumors on withdrawal: Amino acid deficiency shrinks childhood tumors Certain childhood tumors have an extreme need for amino acids. Scientists at the Hopp Children's Cancer Center Heidelberg (KiTZ), the German Cancer Research Center (DKFZ), the University of Heidelberg, and HI-STEM* gGmbH have now discovered the molecular mechanisms underlying this and how the cancer cells could be turned off.https://www.gesundheitsindustrie-bw.de/en/article/press-release/tumors-withdrawal-amino-acid-deficiency-shrinks-childhood-tumors
Press release - 25/04/2022 Reprogrammed macrophages promote spread of breast cancer Metastatic breast cancer cells abuse macrophages, a type of immune cell, to promote the settlement of cancer metastases in the lungs. The reprogrammed macrophages stimulate blood vessel cells to secrete a cocktail of metastasis-promoting proteins that are part of the so-called metastatic niche.https://www.gesundheitsindustrie-bw.de/en/article/press-release/reprogrammed-macrophages-promote-spread-breast-cancer
Peptide-based COVID-19 vaccine - 21/04/2022 CoVac-1: T-cell activator against COVID-19 Current vaccines against COVID-19 aim at forming neutralising antibodies that prevent the virus from penetrating the host cells. Since people with impaired B-cell immune responses – which can also occur in cancer or autoimmune diseases – are not able to do this, researchers at the University of Tübingen have developed the peptide-based T-cell activator CoVac-1, which promises broad and long-term immunity.https://www.gesundheitsindustrie-bw.de/en/article/news/covac-1-t-cell-activator-against-covid-19
Press release - 14/03/2022 Do gut bacteria influence treatment success of CAR-T cell therapies? Through the Endeavour Awards, the Mark Foundation supports research projects that bring together scientists from different disciplines to advance the prevention, diagnosis and treatment of cancer. One of the only four Endeavour Awards presented this year goes to a project coordinated by scientists from the German Cancer Research Center (DKFZ).https://www.gesundheitsindustrie-bw.de/en/article/press-release/do-gut-bacteria-influence-treatment-success-car-t-cell-therapies