A5008727148- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Cancer Immunotherapy and Biomarkers
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Hematopoietic Stem Cell Transplantation
- Polyomavirus and related diseases
- Full-Duplex Wireless Communications
- Systemic Lupus Erythematosus Research
- Antenna Design and Analysis
- Ferroptosis and cancer prognosis
- Sarcoma Diagnosis and Treatment
- CAR-T cell therapy research
- Neutropenia and Cancer Infections
- Acute Myeloid Leukemia Research
- HIV-related health complications and treatments
- Monoclonal and Polyclonal Antibodies Research
- Viral-associated cancers and disorders
- Pneumocystis jirovecii pneumonia detection and treatment
- Cerebrovascular and genetic disorders
- Chronic Lymphocytic Leukemia Research
Neovacs (France)
2016-2019
Agence Nationale de Recherches sur le Sida et les Hépatites Virales
2017
Inserm
2014-2016
Stanford Health Care
2014
Stanford University
2014
Agence Nationale de la Recherche
2014
Cythelia (France)
2012
HIV infection results in CD4+ T cell deficiency, but efficient combination antiretroviral therapy (c-ART) restores cells and decreases morbidity mortality. However, immune restoration by c-ART remains variable, prolonged deficiency a substantial proportion of patients. In prospective open-label phase I/IIa trial, we evaluated the safety efficacy administration regulator IL-7. The trial included 13 c-ART–treated HIV-infected patients whose counts were between 100 400 cells/μl plasma RNA...
Background. The immune deficiency of human immunodeficiency virus (HIV) infection is not fully corrected with ARV therapy. Interleukin-7 (IL-7) can boost CD4 T-cell counts, but optimal dosing and mechanisms cellular increases need to be defined. Methods. We performed a randomized placebo-controlled dose escalation (10, 20 30 µg/kg) trial 3 weekly doses recombinant IL-7 (rhIL-7) in ARV-treated HIV-infected persons counts between 101 400 cells/µL plasma HIV levels <50 copies/mL. Toxicity,...
Objective To evaluate the efficacy and safety of immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial adults with active systemic lupus erythematosus (SLE) despite standard care. Methods Patients SLE (185) moderate to severe disease activity positive interferon (IFN) gene signature were randomised receive IFN-K or PBO intramuscular injections (days 0, 7 28 W12 W24). Coprimary endpoints at W36 neutralisation...
Despite antiretroviral therapy (ART), some HIV-infected persons maintain lower than normal CD4+ T-cell counts in peripheral blood and the gut mucosa. This incomplete immune restoration is associated with higher levels of activation manifested by high systemic biomarkers, including sCD14 D-dimer, that are independent predictors morbidity mortality HIV infection. In this 12-week, single-arm, open-label study, we tested efficacy IL-7 adjunctive on reconstitution mucosa 23 ART suppressed...
<h3>Importance</h3> No reliable treatment options are known for progressive multifocal leukoencephalopathy with underlying immunodeficiency. We describe successful compassionate use of recombinant human interleukin 7 in a patient idiopathic CD4<sup>+</sup>T-cell lymphocytopenia. <h3>Observations</h3> After the diagnoses and lymphocytopenia were established, 61-year-old man was treated on November 1, 2012. Except an episode epilepsia partialis continua January 16, 2013, gradual clinical...
Objective. IFN α Kinoid (IFN-K) is a therapeutic vaccine composed of IFNα2b coupled to carrier protein. In phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the gene signature in whole blood RNA samples from SLE patients. Here, analysed extended follow-up data IFN-K-treated patients, order evaluate persistence neutralizing anti-IFNα Abs antibodies (Abs), and expression profiling.
Progressive multifocal leukoencephalopathy is a currently untreatable infection of the brain. Here, we demonstrate in 2 patients that treatment with interleukin 7, JC polyomavirus (JCV) capsid protein VP1, and Toll-like receptor 7 agonist used as adjuvant, was well tolerated, showed very favorable safety profile unexpected efficacy warrant further investigation.
Background. Phase I/II studies in human immunodeficiency virus (HIV)–infected patients receiving antiretroviral therapy have shown that a single cycle of 3 weekly subcutaneous (s/c) injections recombinant interleukin 7 (r-hIL-7) is safe and improves immune CD4 T-cell restoration. Herein, we report data from 2 phase II trials evaluating the effect repeated cycles r-hIL-7 (20 µg/kg) with objective restoring sustained count >500 cells/µL. Methods. INSPIRE was single-arm trial conducted United...
The heterogeneity of human regulatory T cells (Tregs) may explain the discrepancies between studies on Tregs in physiology and pathology. Contrasting effects IL-7 expansion survival were reported. Therefore, we investigated phenotype function well-characterized populations Tregs. We show that signals via CD127 receptor naive, memory, activated memory sorted from blood healthy donors, but it does not affect their proliferation. In contrast, affects suppressive capacities differently. This...
Abstract In this study, we report the case of a patient with profound lymphopenia after allogenic bone marrow transplantation who developed severe progressive multifocal leukoencephalopathy. Single-agent recombinant human interleukin-7 therapy was associated restoration anti-John Cunningham polyomavirus (JCV) T-cell responses, JCV clearance from cerebrospinal fluid, and dramatic clinical improvement.
Exogenous Interleukin-7 (IL-7), in supplement to antiretroviral therapy, leads a substantial increase of all CD4+ T cell subsets HIV-1 infected patients. However, the quantitative contribution several potential mechanisms action IL-7 is unknown. We have performed mathematical analysis repeated measurements total and naive cells their Ki67 expression from patients involved three phase I/II studies (N = 53 patients). show that, besides transient peripheral proliferation, exerts additional...
Abstract IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. increases total circulating and CD8 counts; however, its effect on HIV-specific cells fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB–mediated costimulation, is lost from chronically stimulated virus-specific with progression of HIV infection humans during chronic lymphocytic choriomeningitis mice. Previous results...
10013 Background: Higher lymphocyte levels correlate with better survival in a variety of cancers, but it remains unclear whether there is causal relationship between immune function and cancer patients. A pilot study high-risk pediatric sarcomas was undertaken to determine if regimen designed enhance reconstitution following standard cytotoxic therapy could improve survival. Methods: Forty-four patients (median 16 yrs, range 5-33) enrolled diagnosis metastatic or late recurrent sarcoma,...
Delays in immune recovery after allo-HSCT are associated with increased risks of infection and relapse. Strategies to enhance T-cell reconstitution could therefore decrease morbidity mortality. Interleukin-7 (IL-7) has a central role T cell development survival. Murine models have shown that IL-7 enhances thymopoiesis peripheral survival expansion. Initial trials recombinant human (rhIL-7) demonstrated dose-dependent expansion CD4+ CD8+ cells patients solid tumors or HIV infection. Hence we...
Abstract Introduction: We previously showed that T (&lt;1000/µl) or CD4 (&lt;450/µl) cell lymphopenia detected before chemotherapy initiation predicts early death for metastatic breast cancer (MBC) patients. ELYPSE-7, a placebo-controlled clinical trial aimed to evaluate impact of CYT107 treatment (before during chemotherapy) on count (see Ray-Coquard abstract). Our ancillary study reports in-depth quantitative and functional changes in circulating immune populations. Methods:...
Abstract Background: Total and CD4 lymphopenia is observed in 25% of advanced cancers patients a predictive factor chemotherapy (CT)-induced death, febrile neutropenia, thrombocytopenia, anemia, as well an independent prognostic for survival tumor progression. CYT107 glycosylated recombinant human IL-7 (CYTHERIS, France) emerging promising immuno-restorative agent tolerated Phase 1 trials. To date, it unknown whether can correct during CT this could translate into clinical benefit cancer...
3033 Background: Lymphopenia is an independent predictive and prognostic factor for chemotherapy (CT)-induced death, febrile neutropenia, overall survival progression in several cancers, including breast carcinoma. CYT107 a glycosylated recombinant human IL-7 (CYTHERIS) able to increase lymphocyte pool man. Whether can correct lymphopenia cancer pts receiving CT improve patient outcome not known. Methods: Using 2x2 factorial design, 20 lymphopenic (<1000/µL) MBC pts, treated with...
Antiretroviral treatment in the last decade of 20th century marked turning tide battle against AIDS.Inspired by patients and staff Positive Care Clinic Atherton, California, artist David Putnam created a triptych to be displayed clinic, illustrating new hope for those affected HIV.The panel on left, centerpiece original triptych, depicts protease inhibitors (blue dots) pitted HIV with its enzyme complex (in black).In right panel, bright yellow background expresses triumph therapy as virus is...
Methods Treg and CD8+ T cells were isolated from healthy donors (n=10) (HD) chronically HAART treated HIV+ pt enrolled in a phase I/II IL-7 INSPIRE study (n=6X) (Levy et al, CID, press). subpopulations (naive CD45RA+FoxP3++CD45RA+CD25++CD127+/-, memory (mTreg) Foxp3highCD45RA-CD25highCD127low, FoxP3++CD45RA-CD25++CD127+/-) cultured with (10 ng/ml). Phenotype (CD39, Bcl-2, Stat5P, purinergic receptor P2X7R), suppression of the proliferation autologous antiCD3 activated (CFSE stained) cytokine...