A5023840270- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Phagocytosis and Immune Regulation
- Genomic variations and chromosomal abnormalities
- Single-cell and spatial transcriptomics
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic function and diabetes
- Glycogen Storage Diseases and Myoclonus
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
- interferon and immune responses
- Cancer Research and Treatments
- Metabolism, Diabetes, and Cancer
University of Amsterdam
2017-2024
Amsterdam University Medical Centers
2018-2024
Oncode Institute
2019-2023
Cancer Center Amsterdam
2019-2023
Institute of Infection and Immunity
2023
Myeloma UK
2022
Lymphoma Research Foundation
2019-2021
Zero to Three
2020
The Netherlands Cancer Institute
2019
Amsterdam UMC Location University of Amsterdam
2017
Autologous T-cell-based therapies, such as chimeric antigen receptor (CAR) T-cell therapy, exhibit low success rates in chronic lymphocytic leukemia (CLL) and correlate with a dysfunctional phenotype observed patients. Despite various proposed mechanisms of dysfunction CLL, the specific CLL-derived factors responsible remain unidentified. This study aimed to investigate through which CLL cells suppress CAR activation function. We found that T get activated, albeit delayed fashion,...
Abstract Acquired T-cell dysfunction is characteristic of chronic lymphocytic leukemia (CLL) and associated with reduced efficacy T cell–based therapies. A recently described feature dysfunctional CLL-derived CD8 cells metabolic plasticity. To what extend CD4 are affected whether metabolism function can be restored upon clinical depletion CLL currently unknown. We address these unresolved issues by comprehensive phenotypic, metabolic, transcriptomic, functional analysis untreated patients...
Hybridoma technology is instrumental for the development of novel antibody therapeutics and diagnostics. Recent preclinical clinical studies highlight importance isotype therapeutic efficacy. However, since sequence encoding constant domains fixed, tuning function in hybridomas has been restricted. Here, we demonstrate a versatile CRISPR/HDR platform to rapidly engineer immunoglobulin obtain recombinant hybridomas, which secrete antibodies preferred format, species, isotype. Using this...
Chronic lymphocytic leukemia (CLL) cells are provided with essential survival and proliferative signals in the lymph node microenvironment. Here, CLL engage various interactions bystander such as T macrophages. Phenotypically distinct types of tumor infiltrating macrophages can either be supportive (M2) or play a role immune surveillance (M1). Although recent vitro findings suggest protective for CLL, actual balance between these macrophage subsets lymphoid tissue is still unclear....
Abstract Immune checkpoint blockade (ICB) has revolutionized cancer therapy, but varying response rates illustrate the need for biomarkers of response. Studies in mice have identified a subset CD8 T cells that is essential to PD‐1 ICB. These co‐express CXCR5, and Tcf1, provide effector upon It unknown whether similar play role ICB humans. We studied human peripheral blood lymph nodes (LNs) frequency, phenotype, functionality CXCR5 + cells. find are memory‐like cells, express lack expression...
Background Interferon (IFN)-β induction via activation of the stimulator interferon genes (STING) pathway has shown promising results in tumor models. STING is activated by cyclic dinucleotides such as GMP–AMP with phosphodiester linkages 2′–5′ and 3′–5′ (cGAMPs), that are produced synthetase (cGAS). However, delivery agonists to site a challenge. Bacterial vaccine strains have ability specifically colonize hypoxic tissues could therefore be modified overcome this Combining high...
Abstract Hybridoma technology is instrumental for the development of novel antibody therapeutics and diagnostics. Recent preclinical clinical studies highlight importance isotype therapeutic efficacy. However, since sequence encoding constant domains fixed, tuning function in hybridomas has been restricted. Here, we demonstrate a versatile CRISPR/HDR platform to rapidly engineer immunoglobulin obtain recombinant which secrete antibodies preferred format, species isotype. Using this platform,...
Background: Chronic lymphocytic leukemia (CLL) patients acquire T cell dysfunction through a yet unresolved mechanism, impeding efficacy of immunotherapeutic strategies. As function and development share an intricate relationship with metabolism, we hypothesized that CLL cells impose reduction in mitochondrial fitness altered glucose metabolism on cells, which may underlie the acquired dysfunction. Aims: We aim to elucidate underlying mechanism intend resolve metabolic via pharmacological...