A5076440275- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- Virus-based gene therapy research
- Complement system in diseases
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Neonatal Respiratory Health Research
- Psoriasis: Treatment and Pathogenesis
- CRISPR and Genetic Engineering
- Viral-associated cancers and disorders
- Phagocytosis and Immune Regulation
- Biomedical Ethics and Regulation
- Biosimilars and Bioanalytical Methods
- Immune cells in cancer
- Pancreatitis Pathology and Treatment
- Streptococcal Infections and Treatments
- CNS Lymphoma Diagnosis and Treatment
- Sepsis Diagnosis and Treatment
- Pediatric health and respiratory diseases
- Histone Deacetylase Inhibitors Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cytomegalovirus and herpesvirus research
- Whipple's Disease and Interleukins
- Adrenal Hormones and Disorders
University Hospital of Zurich
2018-2024
University of Zurich
2020-2024
University Medical Center of the Johannes Gutenberg University Mainz
2014-2015
Johannes Gutenberg University Mainz
2014-2015
University of Michigan
2011-2013
Institute of Medical Microbiology and Hygiene
2013
Universitätsklinikum Erlangen
2013
We investigated how complement activation promotes tissue injury and organ dysfunction during acute inflammation. Three models of lung (ALI) induced by LPS, IgG immune complexes, or C5a were used in C57BL/6 mice, all requiring availability both receptors (C5aR C5L2) for full development ALI. Ligation C5aR C5L2 with triggered the appearance histones (H3 H4) bronchoalveolar lavage fluid (BALF). BALF from humans ALI contained H4 histone. Histones absent control healthy volunteers. In mice ALI,...
Successful vaccination against intracellular pathogens requires the generation of cellular immune responses. Trehalose-6,6-dibehenate (TDB), synthetic analog mycobacterial cord factor trehalose-6,6-dimycolate (TDM), is a potent adjuvant inducing strong Th1 and Th17 We previously identified C-type lectin Mincle as receptor for these glycolipids that triggers FcRγ-Syk-Card9 pathway APC activation adjuvanticity. Interestingly, in vivo data revealed effect was not solely Mincle-dependent but...
Abstract TP53 -mutant acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) are characterized by chemotherapy resistance represent an unmet clinical need. Chimeric antigen receptor (CAR) T-cells might be a promising therapeutic option for AML/MDS. However, the impact of deficiency in AML cells on efficacy CAR is unknown. We here show that engaging -deficient exhibit prolonged interaction time, upregulate exhaustion markers, inefficient to control cell outgrowth vitro vivo compared...
Excessive activation of the complement system is detrimental in acute inflammatory disorders.In this study, we analyzed role complement-derived anaphylatoxins pathogenesis experimental lung injury/acute respiratory distress syndrome (ALI/ ARDS) C57BL/6J mice.Intratracheal administration recombinant mouse component (C5a) caused alveolar inflammation with abundant recruitment Ly6-G + CD11b leukocytes to spaces and severe alveolar-capillary barrier dysfunction (C5a-ALI; EC 50[C5a] = 20 ng/g...
Severe sepsis and septic shock are leading causes of morbidity mortality worldwide. Infection-associated inflammation promotes the development progression adverse outcomes in sepsis. The effects heterodimeric IL-27 (p28/EBI3) have been implicated natural course sepsis, whereas molecular mechanisms underlying regulation gene expression release poorly understood. We studied events regulating p28 subunit endotoxic polymicrobial following cecal ligation puncture. Neutralizing Abs to IL-27(p28)...
Acute lung injury (ALI) is a severe pulmonary disease causing high numbers of fatalities worldwide. Innate immune responses are an integral part the pathophysiologic events during ALI. Interleukin 23 (IL-23) proinflammatory mediator known to direct inflammatory in various settings infection, autoimmunity, and cancer. has been associated with proliferation effector functions T(H)17 cells. Surprisingly, little about production IL-23 In this study, we found expression mRNA for IL-23p19 be...
Highlights•Immunologic conditioning with anti-CD117 antibodies has exhibited efficacy and safety in experimental models clinical trials.•Immunologic could revolutionize the treatment of hematological cancers inherited genetic disorders.•For HSC malignancies, higher effector strength might be provided by modified or CAR T cells.•Complete clearance agents is required before allogeneic stem cell transplantation.AbstractPrecise replacement diseased dysfunctional organs goal regenerative medicine...
The contribution of the adaptive and innate immune systems to pathogenesis outcome sepsis remains a fundamental yet controversial question. Here, we use mice lacking recombination activating gene 1 (Rag-1) study role T B cells in after cecal ligation puncture (CLP). Spleens Rag-1 were atrophic completely devoid CD3 CD19 cells. Wild-type (both on C57BL/6J background) underwent CLP or sham surgery. Both wild-type developed clinical signs within first day CLP. This included severe hypothermia...
The interleukin-17 (IL-17) family of cytokines plays important roles in innate immune defenses against bacterial and fungal pathogens. While much is known about IL-17A, less information available the IL-17F isoform. Here, we investigated gene expression release its regulation by complement system. was produced mouse peritoneal elicited macrophages after TLR4 activation LPS, peaking 12 h. This effect completely dependent on presence adaptor protein MyD88. copresence product, C5a (EC50=10 nM),...
Background Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T therapy in patients with central nervous system (CNS) lymphoma remain limited. Main body We here report occurrence Guillain-Barré-like (GBS) diabetes insipidus (cDI) following tisagenlecleucel for relapsed...
Key Points Human inv(16) AML cells express CSF-1R and are exposed to CSF-1 in vivo. Inhibition of signaling reduces viability vitro therapeutic settings humanized mice
Outbreaks of viral infections, such as measles, are regularly observed and pose a serious threat to recipients allogeneic hematopoietic cell transplantation (HCT). The questions how long cellular humoral protective host immunity persists, whether donor can be transferred has not been clarified. Here we present retrospective analysis immunity-serial antibody titers against mumps, rubella-in 331 patients who underwent HCT at our single center between 2002 2015. Associations the loss levels...
Abstract Acute myeloid leukemia (AML) derives from hematopoietic stem and progenitor cells (HSPCs). To date, no AML‐exclusive, non‐HSPC‐expressed cell‐surface target molecules for AML selective immunotherapy have been identified. Therefore, to still apply surface‐directed in this disease setting, time‐limited combined immune‐targeting of healthy HSPCs, followed by cell transplantation (HSCT), might be a viable therapeutic approach. explore this, we generated recombinant single‐chain variable...
During the entire 20th century, chemotherapy and irradiation were mainstay of non-surgical cancer treatment. In past 20 years, however, immunotherapy has been revolutionizing field oncology with ever-increasing pace. this time, various molecular pathways have successfully exploited to re-direct immune system fight cancer. This shift treatment paradigms was acknowledged by Nobel committee, which awarded 2018 Prize in Physiology or Medicine James Allison Tasuku Honjo for their discoveries...
Background: Acute Myeloid Leukemia (AML) is a clonal disease of the hematopoietic system. Disease relapses are common with current treatment approaches. As an alternative, immunological eradication leukemic cells by adoptively transferred chimeric-antigen receptor T-cells (CAR T-cells) might be considerably more efficient. To date, however, search for AML-specific surface antigens has remained largely elusive. circumvent this problem, we propose to target stem cell antigen c-Kit (CD117) that...