Christina Hesse’s Post

3 days to go until the start of #ATS2024, the international conference of the American Thoracic Society 🫁. 💡Our scientists will present our #lungresearch at the conference, which takes place from May 17 to 22 in San Diego, California ☀️! Don’t miss our poster contributions: 📅 On Sunday, May 19: ▶ Chip cytometry for simultaneous measurement of protein and mRNA markers on single cell level ▶ Effective Pharmacological Modulation of Biomarkers in Lung Tissue of Pulmonary Fibrosis Patients Ex Vivo ▶ Ex Vivo Testing of Antifibrotic Drugs in a Long-term Culture of Precision-cut Lung Slices (PCLS) ▶ Ex-vivo Evaluation of the Potential for Narrow Spectrum Kinase Inhibitors as a Treatment for Idiopathic Pulmonary Fibrosis ▶ CXCL10+ Monocyte-derived Macrophages Are Potential Drivers of TH17.1 Inflammation in Pulmonary Sarcoidosis 📅 On Monday, May 20: ▶ Comprehensive analysis of bronchoalveolar lavage fluid by validating ELISA and MSD systems for 23 biomarkers ▶ Integrated In Vitro/Ex Vivo Assessment of Efficacy and Respiratory Toxicity for Accelerated Respiratory Drug Development ▶ Combined Rhinovirus Infection and Cigarette Smoke Exposure of Normal Human Epithelial Cells and Distal Lung Tissue Ex Vivo Induces Dysregulation of Human Airway Basal Cells 📅 On Tuesday, May 21: ▶ Transcriptomic characterization of type 2 innate lymphoid cells from asthma patients in response to prostaglandin D2 metabolites ▶ Inhaled LNP-formulated siRNA Inhibits Human Parainfluenza Virus Type 3 Infection: From Bench to Bedside ▶ Role of Tumor Necrosis Factor Superfamily Member 10 (TNFSF10) in SARS-CoV2-infection-associated Lung Damage Our colleagues Jens Hohlfeld, Armin Braun, Katherina Sewald, Katharina Schwarz, Sebastian Konzok, Karine Danielyan, CRNA, M.A., MBA, Christina Hesse, Christina Gress, Franziska Dahlmann, Philipp Joel Mroch look forward to meeting you in San Diego! #clinicalresearch #preclinicalresearch

We are part of the impressive American Thoracic Society International Conference 2024 in San Diego. Looking forward meeting you at my posters P499, P958, and P677. #ATS2024 #FraunhoferITEM Don’t miss the other poster contributions of my colleagues: 📅 On Sunday, May 19: ▶ Chip cytometry for simultaneous measurement of protein and mRNA markers on single cell level ▶ Ex Vivo Testing of Antifibrotic Drugs in a Long-term Culture of Precision-cut Lung Slices (PCLS) ▶ Ex-vivo Evaluation of the Potential for Narrow Spectrum Kinase Inhibitors as a Treatment for Idiopathic Pulmonary Fibrosis ▶ CXCL10+ Monocyte-derived Macrophages Are Potential Drivers of TH17.1 Inflammation in Pulmonary Sarcoidosis 📅 On Monday, May 20: ▶ Comprehensive analysis of bronchoalveolar lavage fluid by validating ELISA and MSD systems for 23 biomarkers ▶ Integrated In Vitro/Ex Vivo Assessment of Efficacy and Respiratory Toxicity for Accelerated Respiratory Drug Development ▶ Combined Rhinovirus Infection and Cigarette Smoke Exposure of Normal Human Epithelial Cells and Distal Lung Tissue Ex Vivo Induces Dysregulation of Human Airway Basal Cells 📅 On Tuesday, May 21: ▶ Transcriptomic characterization of type 2 innate lymphoid cells from asthma patients in response to prostaglandin D2 metabolites ▶ Inhaled LNP-formulated siRNA Inhibits Human Parainfluenza Virus Type 3 Infection: From Bench to Bedside ▶ Role of Tumor Necrosis Factor Superfamily Member 10 (TNFSF10) in SARS-CoV2-infection-associated Lung Damage

Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial The 1-year overall survival and progression-free survival were 68% and 32%, respectively. Still need a long-term durability We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were 48.6% for both. The 1-year overall survival and progression-free survival were 68% and 32%, respectively. Patients who achieved OR had higher levels and longer persistence of CAR-NK cells. Receiving CAR-NK cells from a cord blood unit (CBU) with nucleated red blood cells ≤ 8 × 107 and a collection-to-cryopreservation time ≤ 24 h was the most significant predictor for superior outcome. NK cells from these optimal CBUs were highly functional and enriched in effector-related genes. In contrast, NK cells from suboptimal CBUs had upregulation of inflammation, hypoxia and cellular stress programs. https://lnkd.in/efVjA5kz ClinicalTrials.gov identifier: NCT03056339.

In patients with primary biliary cholangitis (PBC), CD8+ tissue-resident memory T cells that highly express programmed cell death protein 1 mediate cytotoxicity against biliary epithelial cells, with PD-1-targeting chimeric antigen receptor (CAR)-T cells shown to specifically deplete CD8+ Trm cells in vivo and to alleviate the disease among mice, according to findings from a study published in the journal Nature Communications. Read more: https://brnw.ch/21wIJgC #RareDisease

While the FDA requests a boxed warning on all commercial autological CAR-T, allogeneic CD19-specific CAR-NK cells have shown a high safety profile and promising efficacy in phase 1/2 trials for patients with B cell malignancies. Researchers at The University of Texas M.D. Anderson Cancer Center have successfully isolated and expanded NK cells from a donor cord blood unit, arming them with an anti-CD19 CAR. Notably, none of the 37 participants in the NCT03056339 clinical trial developed neurotoxicity or graft-versus-host disease, even at maximum tested doses (10 mln cells/kg and a flat dose of 800 mln cells). The day 30 and day 100 overall response rates were both 49%, with 1-year overall survival and progression-free survival rates at 68% and 32%, respectively. Additionally, it was found that the characteristics of the donors’ cord blood units can predict patient outcomes, which could complicate replication and enhance IP protection. These findings offer the potential for safer option for patients with relapsed/refractory CD19-positive B cell malignancies, with significant advantages in logistics, manufacturing, and quality control. Marin, D., Li, Y., Basar, R. et al. Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial. Nat Med (2024). https://lnkd.in/dzP3DS3y     FDA January Safety and Availability Communications: https://lnkd.in/drbe-9GV #BioTechnology #CellTherapy #CARTCellTherapy #CARNKCellTherapy

I am delighted to share this project regarding the modulation of regulatory T cells, published at the beginning of this month. Special thanks to the team, who were always engaged. Lima, A.D.R et al. Dimethyl fumarate modulates the regulatory T cell response in the mesenteric lymph nodes of mice with experimental autoimmune encephalomyelitis. "Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients" https://lnkd.in/ez9_yrWp

Cool study in Nature Communications: PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma https://lnkd.in/dP97ggrN The combination of atezolizumab plus bevacizumab (atezo/bev) has dramatically changed the treatment landscape of advanced HCC (aHCC), achieving durable responses in some patients. Using single-cell transcriptomics, we characterize the intra-tumoural and peripheral immune context of patients with aHCC treated with atezo/bev. Tumours from patients with durable responses are enriched for PDL1+ CXCL10+ macrophages and, based on cell–cell interaction analysis, express high levels of CXCL9/10/11 and are predicted to attract peripheral CXCR3+ CD8+ effector-memory T cells (CD8 TEM) into the tumour. Based on T cell receptor sharing and pseudotime trajectory analysis, we propose that CD8 TEM preferentially differentiate into clonally-expanded PD1- CD45RA+ effector-memory CD8+ T cells (CD8 TEMRA) with pronounced cytotoxicity. In contrast, in non-responders, CD8 TEM remain frozen in their effector-memory state. Finally, in responders, CD8 TEMRA display a high degree of T cell receptor sharing with blood, consistent with their patrolling activity. These findings may help understand the possible mechanisms underlying response to atezo/bev in aHCC.

📚Read in #JEV 📚 The trajectory of vesicular proteomic signatures from HBV-HCC by chitosan-magnetic bead-based separation and DIA-proteomic analysis Lin Cao, Yue Zhou, Shuai Lin, Chunyan Yang, Zixuan Guan, Xiaofan Li, Shujie Yang, Tong Gao, Jiazhen Zhao, Ning Fan, Yanan Song, Dongmin Li, Xiang Li, Zhuo Li, Feng Guan, Zengqi Tan Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS-based magnetic beads (Mag-CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV-HCC patients. Leveraging data-independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV-HCC from CHB, LC, and non-HCC conditions. Collectively, our findings highlight the utility of Mag-CS-based sEV isolation for identifying early detection biomarkers in HBV-HCC. https://lnkd.in/eQhzCK8Z

We are delighted to announce further success in our collaboration with AstraZeneca. Using BenevolentAI’s AI-drug discovery platform, a novel target for systemic lupus erythematosus (SLE) has been identified. 🎯 The target has been experimentally validated by AstraZeneca and added to its discovery portfolio. Following the heart failure milestone, it’s the second target to be selected this year from our extended collaboration. 📣 Prof Maria Belvisi, SVP and Head of Research and Early Development Respiratory and Immunology at AstraZeneca said: “By combining our immunology disease area expertise and BenevolentAI’s AI-driven discovery platform, we are increasing our ability to identify new targets based on patient insights, complementing our portfolio of potential treatments for this debilitating disease.” SLE, or lupus, can cause inflammation, pain and damage – often affecting the organs and joints in severe cases. Extreme fatigue and cognitive issues are also common, along with comorbidities including cardiovascular disease. Read more here: https://lnkd.in/e2mq8haw