A5026333484- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Virus-based gene therapy research
- Blood disorders and treatments
- Immune Cell Function and Interaction
- Prenatal Screening and Diagnostics
- Parvovirus B19 Infection Studies
- T-cell and B-cell Immunology
- Hemoglobinopathies and Related Disorders
- Cytomegalovirus and herpesvirus research
- Tumors and Oncological Cases
- Hematopoietic Stem Cell Transplantation
- Erythrocyte Function and Pathophysiology
- interferon and immune responses
- Autoimmune and Inflammatory Disorders Research
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Neurofibromatosis and Schwannoma Cases
- Acute Myeloid Leukemia Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Chronic Lymphocytic Leukemia Research
Inserm
2014-2025
Institut des Maladies Génétiques Imagine
2015-2025
Université Paris Cité
2014-2025
Assistance Publique – Hôpitaux de Paris
2018-2021
Centre d'Investigation Clinique Biothérapies Necker
2018
Sorbonne Paris Cité
2014-2018
Délégation Paris 5
2014-2016
Hôpital Necker-Enfants Malades
2016
Sickle cell disease is characterized by chronic anemia and vaso-occlusive crises, which eventually lead to multi-organ damage premature death. Hematopoietic stem transplantation the only curative treatment but it limited toxicity poor availability of HLA-compatible donors. A gene therapy approach based on autologous lentiviral-corrected hematopoietic progenitor cells was shown be efficacious in one patient. However, alterations bone marrow environment properties red blood hamper harvesting...
Oncostatin M (OSM) is a cytokine with the unique ability to interact both OSM receptor (OSMR) and leukemia inhibitory factor (LIFR). On other hand, OSMR interacts IL31RA form interleukin-31 receptor. This intricate network of cytokines receptors makes it difficult understand specific function OSM. While monoallelic loss-of-function (LoF) mutations in underlie autosomal dominant familial primary localized cutaneous amyloidosis, vivo consequences human deficiency have never been reported so...
Abstract Reticular dysgenesis is a human severe combined immunodeficiency that primarily characterized by profound neutropenia and lymphopenia. The condition caused mutations in the adenylate kinase 2 (AK2) gene, resulting loss of mitochondrial AK2 protein expression. regulates homeostasis adenine nucleotides (ADP, ATP AMP) catalyzing transfer high-energy phosphate. Our present results demonstrate AK2-knocked-down progenitor cells have poor proliferative survival capacities are blocked their...
Natural Killer (NK) cells hold significant promise as therapeutic agents in immuno-oncology due to their ability target and eliminate cancerous infected without causing graft-versus-host disease or cytokine release syndrome. However, the limited availability of robust, scalable methods for generating clinical-grade NK remains a limiting factor broader clinical application. Here we report development novel feeder-cell-free culture system optimized producing from cord blood-derived CD34+...
Severe combined immunodeficiencies (SCIDs) constitute a heterogeneous group of life-threatening genetic disorders that typically present in the first year life. They are defined by absence autologous T cells and presence an intrinsic or extrinsic defect B-cell compartment. In three newborns presenting with frequent infections profound leukopenia, we identified private, heterozygous mutation RAC2 gene (p.G12R). This was de novo index case, who had been cured hematopoietic stem cell...
Autologous transplantation of hematopoietic stem cells transduced with a lentiviral vector (LV) expressing an anti-sickling HBB variant is potential treatment for sickle cell disease (SCD). With clinical trial as our ultimate goal, we generated LV constructs containing transgene (HBBAS3), minimal promoter, and different combinations DNase I hypersensitive sites (HSs) from the locus control region (LCR). Hematopoietic progenitor (HSPCs) SCD patients were LVs either HS2 HS3 (β-AS3) or HS2,...
Abstract T cells represent a valuable tool for treating cancers and infectious inherited diseases; however, they are mainly short-lived in vivo. T-cell therapies would strongly benefit from gene transfer into long-lived persisting naive or progenitors. Here we demonstrate that baboon envelope glycoprotein pseudotyped lentiviral vectors (BaEV-LVs) far outperformed other LV pseudotypes transduction of adult fetal interleukin-7–stimulated cells. Remarkably, BaEV-LVs efficiently transduced...
Recombinase-activating gene (RAG)-deficient SCID patients lack B and T lymphocytes due to the inability rearrange immunoglobulin cell receptor genes. The two RAG genes act as a required dimer initiate recombination. Gene therapy is valid treatment alternative for RAG-SCID who suitable bone marrow donor, but developing such RAG1/2 has proven challenging. Using clinically approved lentiviral vector with codon-optimized RAG1 gene, we report here preclinical studies using CD34+ cells from four...
Adaptive immunity relies on an efficient lymphocyte response, enabling organism to defend itself against infections or malignancies. Lymphocyte repertoire may be impacted by various factors, including conditions such as primary immune deficiencies Acquired Immunodeficiency Syndrome (AIDS), treatments chemotherapy
Gene therapy for SCID and CID usually leads to a more efficient T-cell reconstitution as compared HSCT from mismatched related donor. However, observed in ADA, X1 WAS gene trials, T cell recovery is sometimes slow associated with morbidity mortality due viral infections. In order shorten post-transplant immunodeficiency reduce the frequency of these complications, one possible strategy transplant gene-corrected committed precursors. We have recently set up protocol transplanting...