A5048543389- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Renal Transplantation Outcomes and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Xenotransplantation and immune response
- Chemokine receptors and signaling
- Diabetes and associated disorders
- Immune Response and Inflammation
- Acute Lymphoblastic Leukemia research
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Systemic Lupus Erythematosus Research
- Inflammatory Bowel Disease
- Animal Genetics and Reproduction
- Ferroptosis and cancer prognosis
- Salivary Gland Disorders and Functions
- Hepatitis B Virus Studies
- Organ Transplantation Techniques and Outcomes
OSE Immunotherapeutics (France)
2016-2025
Université de Montréal
2024
Centre Hospitalier Universitaire Sainte-Justine
2024
German University in Cairo
2019
Institut de Transplantation Urologie en Nephrologie
2007-2018
Inserm
2008-2018
Nantes Université
2008-2018
Centre d'Investigation Clinique de Nantes
2016-2018
Center for Research in Transplantation and Translational Immunology
2016-2018
Centre Hospitalier Universitaire de Nantes
2011-2016
Abstract The immune tolerance to rat kidney allografts induced by a perioperative treatment with anti-CD28 Abs is associated severe unresponsiveness of peripheral blood cells donor Ags. In this model, we identified an accumulation in the CD3−class II−CD11b+CD80/86+ plastic-adherent that additionally expressed CD172a as well other myeloid markers. These were able inhibit proliferation, but not activation, effector T and induce apoptosis contact-dependent manner. Their suppressive action was...
An improved method of immunosuppression allows better immune function and prolongs the survival transplanted organs in nonhuman primates.
It remains unknown what causes inflammatory bowel disease (IBD), including signaling networks perpetuating chronic gastrointestinal inflammation in Crohn's (CD) and ulcerative colitis (UC), humans. According to an analysis of up 500 patients with IBD 100 controls, we report that key transcripts the IL-7 receptor (IL-7R) pathway are accumulated inflamed colon tissues severe CD UC not responding either immunosuppressive/corticosteroid, anti-TNF, or anti-α4β7 therapies. High expression both...
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature that believed to inhibit immune responses in the contexts cancer and organ transplantation, association with regulatory T (Treg). However, way which MDSC cooperate Treg remains elusive. In this study, we used DNA microarrays analyze gene expression blood-derived from rat recipients kidney allografts. We found CCL5 (Rantes), chemotactic C-C motif 5 chemokine, be strongly downregulated after treatment tolerizing...
Selective targeting of CD28 might represent an effective immunomodulation strategy by preventing T cell costimulation, while favoring coinhibition since inhibitory signals transmitted through CTLA-4; PD-L1 and B7 would not be affected. We previously showed in vitro vivo that anti-CD28 antagonists suppress effector cells enhancing regulatory (Treg) suppression immune tolerance. Here, we evaluate FR104, a novel antagonist pegylated Fab' antibody fragment, nonhuman primate renal...
Targeting the expansion of pathogenic memory immune cells is a promising therapeutic strategy to prevent chronic autoimmune attacks. Here we investigate efficacy and mechanism new anti-human IL-7Rα monoclonal antibodies (mAb) in non-human primates show that, depending on target epitope, single injection antagonistic anti-IL-7Rα mAbs induces long-term control skin inflammation despite repeated antigen challenges presensitized monkeys. No modification T cell numbers, phenotype, function or...
T cell exclusion causes resistance to cancer immunotherapies via immune checkpoint blockade (ICB). Myeloid cells contribute by expressing signal regulatory protein-α (SIRPα), an inhibitory membrane receptor that interacts with ubiquitous CD47 control macrophage phagocytosis in the tumor microenvironment. Although CD47/SIRPα-targeting drugs have been assessed preclinical models, therapeutic benefit of selectively blocking SIRPα, and not SIRPγ/CD47, humans remains unknown. We report a potent...
Agonistic proresolutive monoclonal antibody reverses chronic inflammation.
Antagonist anti-CD28 antibodies prevent T cell costimulation and differentiate from CTLA4Ig since they cannot block CTLA-4 PDL-1 coinhibitory signals. They demonstrated efficacy in suppressing effector cells while enhancing regulatory function immune tolerance. However, devoid of immunotoxicity with a good pharmacokinetic profile have not yet been developed. Here, we describe FR104, novel humanized pegylated Fab' antibody fragment presenting long elimination half-life monkeys. In vitro,...
CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive negative costimulatory molecules that, among other functions, control T cell motility formation of immune synapse between cells antigen-presenting (APCs). What remains incompletely understood is how CD28 leads to activation effector (Teff) but inhibition suppression by regulatory (Tregs), while PD-L1 inhibit Teff function crucial suppressive Tregs. Using alloreactive human blocking antibodies, we show here...
Belatacept is a biologic that targets CD80/86 and prevents its interaction with CD28 alternative ligand, cytotoxic T lymphocyte antigen 4 (CTLA-4). Clinical experience in kidney transplantation has revealed high incidence of rejection belatacept, especially intensive regimens, suggesting blocking CTLA-4 deleterious. We performed head to assessment FR104 ( n =5), selective pegylated Fab′ antibody fragment antagonist does not block the pathway, belatacept =5) allotransplantation baboons. The...
Abstract FR104 is a monovalent pegylated Fab′ Ab, antagonist of CD28, under development for treatment transplant rejection and autoimmune diseases. In contrast to CD80/86 antagonists (CTLA4-Ig), selectively blunts CD28 costimulation while sparing CTLA-4 PD-L1 coinhibitory signals. the present work, has been evaluated in first-in-human study evaluate safety, pharmacokinetics, pharmacodynamics, potency i.v. administrations healthy subjects. Sixty-four subjects were randomly assigned four...
Controlling graft-versus-host disease (GVHD) remains a major unmet need in stem cell transplantation, and new, targeted therapies are being actively developed. CD28-CD80/86 costimulation blockade represents promising strategy, but targeting CD80/CD86 with CTLA4-Ig may be associated undesired of coinhibitory pathways. In contrast, CD28 exclusively inhibits T more potently prevent GVHD. Here, we investigated FR104, an antagonistic CD28-specific pegylated-Fab′, the nonhuman primate (NHP) GVHD...
Objective Primary Sjögren’s syndrome (SS) is characterized by a lymphocytic infiltration of salivary glands (SGs) and the presence an interferon (IFN) signature. SG epithelial cells (SGECs) play active role in primary SS pathophysiology. We undertook this study to examine interactions between SGECs T interleukin‐7 (IL‐7)/IFN axis. Methods cultured from control subjects patients with were stimulated poly(I‐C), IFNα, or IFNγ. sorted blood IL‐7. CD25 expression was assessed flow cytometry....
Abstract Background The signaling networks perpetuating chronic inflammatory bowel disease remain unclear. Interleukin-7 (IL-7) has been previously reported to trigger the expansion of effector Th17 cells and anti-IL-7 receptor (IL-7R) antagonism render IL23-differentiated susceptible apoptosis1. We that IL-7R pathway is locally dysregulated over-expressed in colon mucosa severe IBD patients reproducibly associated with unresponsiveness anti-TNF or anti-α4β7 integrin therapies2. developed a...
Abstract Costimulatory and coinhibitory receptor–ligand pairs on T cells APC control the immune response. We have investigated whether selective blockade of CD28–CD80/86 costimulatory interactions, which preserves CTLA4–CD80/86 interactions function regulatory (Treg) cells, abrogates induction experimental autoimmune encephalomyelitis (EAE) in rhesus monkeys. EAE was induced by intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) CFA day 0. FR104 is...
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature hematopoietic precursors known to suppress immune responses. Interaction SIRP alpha (SIRPα), expressed by myeloid cells, with the ubiquitous receptor CD47 is an important checkpoint innate response regulating macrophages and dendritic functions. We previously described that MDSC expressing SIRPα accumulated after transplantation maintained kidney allograft tolerance. However, role SIRPα/CD47 axis on function...
A numerous number of positive and negative signals via various molecules modulate T-cell activation. Within the transmembrane proteins, SIRPγ is interest since it not expressed in rodents. interaction with CD47 reevaluated this study. Indeed, we show that anti-SIRPγ mAb clone LSB2.20 previously used by others has been appropriately characterized. We reveal anti-SIRPα KWAR23 a Pan anti-SIRP which efficiently blocks SIRPα interactions CD47. expression on T cells varies their differentiation...