VERHOEYEN , Els

Over the last decade, incrementally improved xenograft mouse models, which support the engraftment and development of a human hemato-lymphoid system, have been developed and represent an important fundamental and preclinical research tool. Immunodeficient mice can be transplanted with human hematopoietic stem cells (HSCs) and this process is...

Since they allow gene integration into their host genome, lentiviral vectors (LVs) have strong therapeutic potentials, as emphasized by recent clinical trials. The surface-display of the pantropic vesicular stomatitis virus G glycoprotein (VSV-G) on LVs resulted in powerful tools for fundamental and clinical research. However, improved LVs are...

Cyclic dinucleotides, a class of microbial messengers, have been recently identified in bacteria, but their activity in humans remains largely unknown. Here, we have studied the function of cyclic dinucleotides in humans. We found that c-di-AMP and cGAMP, two adenosine-based cyclic dinucleotides, activated T lymphocytes in an unusual manner...

Immunotherapy strategies aim to mobilize immune defenses against tumor cells by targeting mainly T cells. Co‐inhibitory receptors or immune checkpoints (ICPs) (such as PD-1 and CTLA4) can limit T cell receptor (TCR) signal propagation in T cells. Antibody-based blocking of immune checkpoints (immune checkpoint inhibitors, ICIs) enable escape...

International audience

Human CD21low B cells present with an activated phenotype and accumulate in distinct disorders connected with chronic immune stimulation. Signaling studies had revealed an increased basal phosphorylation of spleen tyrosine kinase (SYK) and phospholipase Cγ2. Additional BCR stimulation of these constitutively active cells, however, led to...

International audience

International audience

International audience

Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector...

Cyclic dinucleotides are important messengers for bacteria and protozoa and are well-characterized immunity alarmins for infected mammalian cells through intracellular binding to STING receptors. We sought to investigate their unknown extracellular effects by adding cyclic dinucleotides to the culture medium of freshly isolated human blood...

The development of lentiviral vectors (LVs) for expression of a specific antibody can be achieved through the transduction of mature B-cells. This approach would provide a versatile tool for active immunotherapy strategies for infectious diseases or cancer, as well as for protein engineering. Here, we created a lentiviral expression system...

T-cell acute lymphoblastic leukemia (TALL) represents expansion of cells arrested at specific stages of thymic development with the underlying genetic abnormality often determining the stage of maturation arrest. Although their outcome has been improved with current therapy, survival rates remain only around 50% at 5 years and patients may...

IRE1α is one of the three ER transmembrane transducers of the Unfolded Protein Response (UPR) activated under endoplasmic reticulum (ER) stress. IRE1α activation has a dual role in cancer as it may be either pro- or anti-tumoral depending on the studied models. Here, we describe the discovery that exogenous expression of IRE1α, resulting in...

Essentials B cells are attractive targets for gene therapy and particularly interesting for immunotherapy. A baboon envelope pseudotyped lentiviral vector (BaEV-LV) was tested for B-cell transduction. BaEV-LVs transduced mature and plasma human B cells with very high efficacy. BaEV-LVs allowed secretion of functional factor IX from B cells at...

Whether cancer is maintained by a small number of stem cells or is composed of proliferating cells with approximate phenotypic equivalency is a central question in cancer biology. In the stem cell hypothesis, relapse after treatment may occur by failure to eradicate cancer stem cells. Chronic myeloid leukaemia (CML) is quintessential to this...

Activated B cell diffuse large B cell lymphoma (ABC-DLBCL) is an aggressive lymphoproliferative disorder involving chronic NF-κB activation. Several mutations in the BCR and the MyD88 signaling pathway components, such as MyD88 L265P, are implicated in this aberrant activation. Among heat-shock proteins, HSP110 has recently been identified as a...

Playing a central role in both innate and adaptive immunity, CD4(+) T cells are a key target for genetic modifications in basic research and immunotherapy. In this article, we describe novel lentiviral vectors (CD4-LV) that have been rendered selective for human or simian CD4(+) cells by surface engineering. When applied to PBMCs, CD4-LV...

The recombination activating gene (RAG) 1 and RAG2 protein complex introduces DNA breaks at Tcr and Ig gene segments that are required for V(D)J recombination in developing lymphocytes. Proper regulation of RAG1/2 expression safeguards the ordered assembly of Ag receptors and the development of lymphocytes, while minimizing the risk for...

CSF-1 and IL-34 share the CSF-1 receptor and no differences have been reported in the signaling pathways triggered by both ligands in human monocytes. IL-34 promotes the differentiation and survival of monocytes, macrophages and osteoclasts, as CSF-1 does. However, IL-34 binds other receptors, suggesting that differences exist in the effect of...

Background The success and limitations of current immunotherapies have pushed research toward the development of alternative approaches and the possibility to manipulate other cytotoxic immune cells such as natural killer (NK) cells. Here, we targeted an intracellular inhibiting protein 'cytokine inducible SH2-containing protein' (CISH) in NK...

Hematopoietic transitions that accompany fetal development, such as erythroid globin chain switching, play important roles in normal physiology and disease development. In the megakaryocyte lineage, human fetal progenitors do not execute the adult morphogenesis program of enlargement, polyploidization, and proplatelet formation. Although these...

International audience

International audience