A5100330540- CAR-T cell therapy research
- RNA modifications and cancer
- Cancer-related gene regulation
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Erythrocyte Function and Pathophysiology
- Biosimilars and Bioanalytical Methods
- Viral Infectious Diseases and Gene Expression in Insects
- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Genomics and Chromatin Dynamics
- NF-κB Signaling Pathways
- CRISPR and Genetic Engineering
- Acute Lymphoblastic Leukemia research
- Cytokine Signaling Pathways and Interactions
University Hospital Heidelberg
2021-2024
Heidelberg University
2020-2024
European Molecular Biology Organization
2022-2023
Shenzhen Children's Hospital
2023
Wuhan University
2023
Renmin Hospital of Wuhan University
2023
Genmab (United States)
2023
European Molecular Biology Laboratory
2021
UCLA Health
2018
Cornell University
2016
Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual stem might lead an insufficient graft-versus-leukemia (GVL) effect relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) lymphocytes CD34+ 6 patients with AML 100 days after allo-HCT identify T-cell signatures...
The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity vivo. A comprehensive analysis the rRNA landscape 94 patients with acute myeloid (AML) revealed dynamic specifically at exterior sites ribosomes. pattern is closely associated AML stage LSC gene expression signature. Forced 2'-O-methyltransferase...
Abstract Non-small cell lung cancer (NSCLC) is the leading cause of death worldwide underlining urgent need for new biomarkers and therapeutic targets this disease. Long noncoding RNAs are critical players in NSCLC but role small RNA species not well understood. In present study, we investigated H/ACA box nucleolar (snoRNAs) snoRNA-bound ribonucleoproteins (snoRNPs) tumorigenesis NSCLC. snoRNPs including NOP10 core protein were highly expressed High levels either mRNA or associated with poor...
Objectives: To understand the clinical relationship between PRMT5 and cancer, to explore an accurate prediction of a cancer patient’s survival response individualized treatment therapy. Methods: We analyzed data from The Cancer Genome Atlas (TCGA) in comparison with previous preclinical studies on PRMT5. Gene Expression Profiling Interactive Analysis (GEPIA) was utilized investigate correlation expression clinicopathologic information lymphoma. GSEA used detect pathways which genes are...
Immunotherapies, such as chimeric antigen receptor (CAR) modified T cells and antibody-drug conjugates (ADCs), have revolutionized the treatment of cancer, especially lymphoid malignancies. The application targeted immunotherapy to patients with acute myeloid leukemia (AML) has been limited in particular by lack a tumor-specific target antigen. Gemtuzumab ozogamicin (GO), an ADC targeting CD33, is only approved immunotherapeutic agent AML. In our study, we introduce CD33-directed...
Abstract Purpose: The use of costimulatory molecules targeting distinct T-cell signaling pathways has provided a means for triggering and enhancing antitumor immunity; however, it is still not fully understood what types are suitable the combination in tumor therapy. Our purpose this study to establish an effective immune approach by using molecule 4-1BBL with soluble PD-1. Experimental Design: murine H22 hepatocarcinoma served as ectopic model. Local gene transfer was done injection naked...
Relapsed and refractory acute myeloid leukemia (AML) carries a dismal prognosis. CAR T cells have shown limited efficacy in AML, partially due to dysfunctional autologous the extended time for generation of patient specific cells. Allogeneic NK cell therapy is promising alternative, but strategies enhance persistence may be necessary. Proteasome inhibitors (PI) induce changes surface proteome which render malignant more vulnerable mediated cytotoxicity. Here, we investigated potential...
Introduction: Outcomes are poor for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Effective treatments that drive deep, durable responses and long-term benefit needed. In the pivotal EPCORE™ NHL-1 trial (NCT03625037), single-agent epcoritamab showed high complete response (CR) MRD-negativity rates a manageable safety profile as an off-the-shelf, subcutaneous, CD3xCD20 T-cell–engaging bispecific antibody (Thieblemont et al. J Clin Oncol, 2022). We present updated...
<title>Abstract</title> RNA constitutes a large fraction of chromatin. Spatial distribution and functional relevance associating with chromatin remain largely elusive. We established landscape analysis RNA-chromatin interactions in human acute myeloid leukemia (AML). In total more than 50 million were captured an AML cell line. Protein-coding mRNAs long non-coding RNAs (lncRNAs) exhibited substantial number <italic>cis</italic>-interactions suggesting transcriptional activity. contrast,...
<div>Abstract<p>The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, functional evidence that dynamics in ribosomal RNA (rRNA) 2′-O-methylation regulate leukemia stem cell (LSC) activity <i>in vivo</i>. A comprehensive analysis the rRNA landscape 94 patients with acute myeloid (AML) revealed dynamic specifically at exterior sites ribosomes. The pattern is closely associated AML stage LSC gene...
Signals provided by the microenvironment can modify and circumvent pathway activities that are therapeutically targeted drugs. Bone marrow stromal cell coculture models frequently used to study influence of bone niche on ex vivo drug response. Here, we show mesenchymal cells from selected donors NKTert, a line, which is commonly for studies with primary leukemia cells, extensively phagocytose apoptotic cells. This could lead misinterpretation results, especially if viability readouts target...
Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable success in treating hematological malignancies. However, CAR-T for solid tumors is still limited due to the unique solid-tumor microenvironment and heterogeneous target expression, which leads an urgent need of combining other therapies. At present, nano delivery system become one most promising directions development anti-tumor drugs. Based on background tumor treatment, we focus research progress nanomedicine combined...
Abstract Although T-cell-engaging therapies are highly effective in patients with relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL), responses often not durable. To identify tumor-intrinsic drivers of resistance, we quantified in-vitro response to CD19-directed chimeric antigen receptor T-cells (CD19-CAR) and bispecific antibodies (BsAb) across 46 B-NHL cell lines measured their proteomic profiles at baseline. Among the proteins associated poor was Serpin B9, an endogenous...
Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: (AML) is a particularly aggressive age-related malignancy characterized by abnormal hematopoietic differentiation and aberrant epigenetic driver mutations. Patients treated with the standard of care experience low response rates, high levels relapse an overall poor prognosis due to resistance. Chimeric antigen receptor (CAR) T cells directed towards cell surface proteins are being explored in AML but have shown...
Abstract Background Blinatumomab could be successfully used to reduce minimal residual disease (MRD) prior hematopoietic stem cell transplantation (HSCT) in pediatric B precursor acute lymphoblastic leukemia (BCP-ALL), but sound evidence is lacking China. Case presentation This retrospective study assessed the application of blinatumomab B-ALL accompanied by persistent or relapsed low-level MRD before HSCT from April 2019 July 2021. Two cases (Cases 1 and 2) initially achieved remission with...
<div>Abstract<p>The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, functional evidence that dynamics in ribosomal RNA (rRNA) 2′-O-methylation regulate leukemia stem cell (LSC) activity <i>in vivo</i>. A comprehensive analysis the rRNA landscape 94 patients with acute myeloid (AML) revealed dynamic specifically at exterior sites ribosomes. The pattern is closely associated AML stage LSC gene...
<p>Supplementary Figure S1 shows enrichment of FBL in LSC, correlation with LSC signature and rRNA 2'-O-Me healthy hematopoietic cells. Supplementary S2 the association 2’-O-Me differentiation signatures. S3 strategy for sorting distribution methylation sites on ribosomes. S4 effect knockdown 2’-O-methylation vitro proliferation leukemia S5 show overexpression vivo engraftment primary AML S6 nascent proteome metabolism S7 ribosome footprinting analysis after knockdown. S8 Gm1447...
<p>Supplementary Figure S1 shows enrichment of FBL in LSC, correlation with LSC signature and rRNA 2'-O-Me healthy hematopoietic cells. Supplementary S2 the association 2’-O-Me differentiation signatures. S3 strategy for sorting distribution methylation sites on ribosomes. S4 effect knockdown 2’-O-methylation vitro proliferation leukemia S5 show overexpression vivo engraftment primary AML S6 nascent proteome metabolism S7 ribosome footprinting analysis after knockdown. S8 Gm1447...
Introduction: Treatment options for relapsed or refractory (r/r) B-cell non-Hodgkin lymphomas (B-NHL) have broadened towards T-cell engaging therapies, including CD19-targeting chimeric antigen receptor T-cells (CD19-CAR) and bispecific antibodies (CD19-BsAb). Although CD19-CAR CD19-BsAb induce durable responses in some r/r B-NHL patients, response remains heterogenous a significant proportion of patients experience insufficient relapse. A thorough understanding tumor-intrinsic mechanisms...