A5089749394- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Phagocytosis and Immune Regulation
- Immunodeficiency and Autoimmune Disorders
- Angiogenesis and VEGF in Cancer
- 14-3-3 protein interactions
- Acute Myeloid Leukemia Research
- Lymphoma Diagnosis and Treatment
- Cellular transport and secretion
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- HER2/EGFR in Cancer Research
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- Atherosclerosis and Cardiovascular Diseases
- Ubiquitin and proteasome pathways
- Erythrocyte Function and Pathophysiology
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Lymphatic System and Diseases
- Systemic Lupus Erythematosus Research
- Multiple Myeloma Research and Treatments
Max Delbrück Center
2014-2024
Charité - Universitätsmedizin Berlin
2004-2016
Medizinische Hochschule Hannover
2000
Massachusetts Institute of Technology
1997
Center for Cancer Research
1997
SorLA has been recognized as a novel sorting receptor that regulates trafficking and processing of the amyloid precursor protein (APP) represents significant risk factor for sporadic Alzheimer disease. Here, we investigated cellular mechanisms control intracellular sorLA their relevance APP processing. We demonstrate acts retention in trans-Golgi compartments/trans-Golgi network, preventing release into regular pathways. Proper localization activity are dependent on functional interaction...
Chimeric antigen receptor (CAR) redirected T cells are potent therapeutic options against hematological malignancies. The current dominant manufacturing approach for CAR depends on retroviral transduction. With the advent of gene editing, insertion a CD19-CAR into cell (TCR) alpha constant (TRAC) locus using adeno-associated viruses transfer was demonstrated, and these showed improved functionality over their retrovirally transduced counterparts. However, clinical-grade production is complex...
Abstract Allogeneic natural killer (NK) cell adoptive transfer is a promising treatment for several cancers but less effective the of multiple myeloma. In this study, we report on quadruple gene-engineered induced pluripotent stem (iPSC)-derived NK cells designed mass production from renewable source and dual targeting against myeloma through introduction an cell-optimized chimeric antigen receptor (CAR) specific B maturation (BCMA) high affinity, non-cleavable CD16 to augment...
In human chronic lymphocytic leukemia (CLL) pathogenesis, B-cell antigen receptor signaling seems important for ontogeny, whereas the microenvironment influences activation, tumor cell lodging, and provision of antigenic stimuli. Using murine Eμ-Tcl1 CLL model, we demonstrate that CXCR5-controlled access to follicular dendritic cells confers proliferative stimuli B cells. Intravital imaging revealed a marginal zone cell-like trafficking route. Murine reciprocally stimulated resident...
Abstract CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B leukemia, however shows less efficacy lymphoma with nodal dissemination. To target both Non-Hodgkin’s (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 high avidity. CXCR5, physiologically expressed on mature Tfh cells, is also highly B-NHLs. Anti-CXCR5 eradicate B-NHL lymphoma-supportive more...
Autologous T cells genetically modified with a chimeric antigen receptor (CAR) redirected at CD19 have potent activity in the treatment of B cell leukemia and non-Hodgkin's lymphoma (B-NHL). Immunotherapies to treat multiple myeloma (MM) targeted maturation (BCMA), which is expressed most cases MM. We developed humanized CAR specificity for BCMA based on our previously generated anti-BCMA monoclonal antibody. The targeting single-chain variable fragment (scFv) domain exhibited binding...
Human cytomegalovirus encodes the G protein-coupled chemokine receptor homologue US28 that binds several CC chemokines and sequesters extracellular from environment of infected cells. Mechanistically, it has been shown undergoes rapid constitutive endocytosis recycling. Monoclonal antibodies were raised allowed characterization a ligand-independent phosphorylation low surface expression in transiently transfected HEK293A Phosphoamino acid analysis defined C-terminal serine threonine residues...
Human cytomegalovirus (HCMV) encodes several proteins that inhibit major histocompatibility complex (MHC) class I-dependent antigen presentation. The HCMV products US2 and US11 are each sufficient for causing the dislocation of human murine MHC I heavy chains from lumen endoplasmic reticulum to cytosol, where readily degraded. apparent redundancy has been probed predominantly in cultured cell lines, differences their specificities were shown locus products. Here, we expressed via adenovirus...
Recruitment of tumor-associated macrophages and neutrophils (TAM TAN) to solid tumors contributes immunosuppression in the tumor microenvironment; however, their contributions lymphoid neoplasms are less clear. In human chronic lymphocytic leukemia (CLL), B cells lodge lymph nodes where interactions with microenvironment occur. Tumor cell homing stimulates proliferation, such that engagement B-cell receptor is important for malignant progression. Eμ-Tcl1 murine model CLL, we identified gene...
Tumor immunology has received a large impetus from the identification of tumor-associated antigens. Among them, monoclonal antibody, 22.1.1, was instrumental in defining novel antigen that termed "receptor binding cancer expressed on SiSo cells" (RCAS1). RCAS1 proposed to induce growth arrest and apoptosis activated immune cells, mediated by putative death receptor. Structurally, predicted exist as type II transmembrane protein soluble form. Here, we analyzed occurrence, membrane topology,...
Interleukin 17-producing helper T (Th17) cells have been widely defined by the lineage transcription factor retinoid-related orphan receptor (ROR)γt. Pathophysiologically, these play a crucial role in autoimmune diseases and linked to dysregulated germinal center (GC) reactions autoantibody production. In this study, we used gene expression flow cytometric analyses for characterization of Rorγt–/– Rorγt–/–Il21RFP/+ mice demonstrate previously unknown transcriptional flexibility development...
Dendritic cells (DC) either induce T cell tolerance or contribute to the initiation and modulation of B responses. Since many variables determining thresholds naive priming were defined in vitro using a homogeneously matured DC population, we here focused on partially mature which might reflect occurrence tumor-infiltrating thymic DC. To predict how those regulate induction antigen-specific proliferation tolerance, co-cultured ovalbumin-pulsed murine at different ratios with DO11.10...
The advent of CAR T cells targeting CD19 or BCMA on B cell neoplasm demonstrated remarkable efficacy, but rapid relapses and primary refractoriness remains challenging. A leading cause failure is their lack expansion limited persistence. Long-lived, self-renewing multipotent memory stem (TSCM) central (TCM) likely sustain superior tumor regression, low frequencies in blood from cancer patients impose a major hurdle for clinical production. We designed clinically compliant protocol generating...
Regulated exocytosis is subject to several modulatory steps that include phosphorylation events and transient protein-protein interactions. The estrogen receptor-binding fragment-associated gene9 (EBAG9) gene product was recently identified as a modulator of tumor-associated O-linked glycan expression in nonneuronal cells; however, this molecule expressed physiologically essentially all mammalian tissues. Particular interest has developed toward because some human tumor entities high levels...
The UT-A1 urea transporter mediates rapid transepithelial transport across the inner medullary collecting duct and plays a major role in urinary concentrating mechanism. To urea, must be present plasma membrane. purpose of this study was to screen for UT-A1-interacting proteins interactions one identified potential binding partners with UT-A1. Using yeast two-hybrid human kidney cDNA library intracellular loop (residues 409-594) as bait, we snapin, ubiquitously expressed SNARE-associated...
Coxsackievirus B3 (CVB3)-infection is a frequent cause of acute myocarditis, which may result in chronic myocarditis and virus persistence. Investigation the initial immune responses to CVB3 shed light on mechanisms that contribute ongoing disease. DCs, as key professional APCs, were investigated two MHC-matched hosts: while C57BL/6 mice are resistant CVB3-myocarditis, A.BY/SnJ mouse strain exhibits susceptibility. DC maturation activation critically impaired mice, reflected by failure DCs...